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Toshiyuki Takai

Section

Institute of Development, Aging and Cancer

Job title

Specially Appointed Professor(Research)

Degree

医学博士（京都大学）
薬学修士（岡山大学）

researchmap

https://researchmap.jp/toshiyukiTAKAI_SD

J-GLOBAL ID

200901077835231225

Profile

略歴
昭和33年岡山県生まれ
昭和55年岡山大学薬学部卒業
昭和61年京都大学大学院医学研究科修了医学博士
昭和61年国立循環器病センター研究所研究員
昭和63年岡山大学工学部生物応用工学科助手
平成元年同講師
平成2年同助教授
平成4〜5年米国スローン・ケタリング研究所訪問研究員（文部省在外研修として）
平成9年東北大学加齢医学研究所教授

令和5年同　特任教授（研究）

受賞
平成16年第7回日本免疫学会賞
平成24年文部科学大臣表彰科学技術賞（研究部門）

Research History 1

2023/04 - Present

Tohoku University　Institute of Development, Aging and Cancer Division of Gene Research Experimental Immunology　Specially Appointed Professor (Research)

Education 2

Kyoto University　Graduate School, Division of Medicine　生理系

- 1986/03
Okayama University　Faculty of Pharmaceutical Science　製薬化学

- 1980/03

Committee Memberships 7

International Immunology　編集委員

2002/04 - Present
日本免疫学会　評議員

2008/10 - 2023/09
日本生化学会　評議員

1998/04 - 2021/03
日本免疫学会　理事

2016/10 - 2018/09
Europeal Journal Immunology　編集委員

2001/04 - 2003/03
東北医学会　評議員

1998/04 - 1999/03
東北医学会　評議員

1998/04 - 1999/03

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Professional Memberships 14

日本生化学会(1998/04- 評議員)

1998/04 - 2021/03
日本免疫学会(2008/10- 評議員)
日本学術振興会(2005/04-2007/03 専門委員)
Europeal Journal Immunology(2001/04- 編集委員)
International Immunology(2002/04- 編集委員)
Springer Seminars in Immunopathology(2007/04- 顧問)
東北医学会(1998/04-1999/03 評議員)
免疫と疾患研究会(1998/04- 世話人)
東北免疫研究会(1999/04- 顧問)
American Association of Immunologists(1993/04-)
日本再生医学会(1995/04-)
日本アレルギー学会(1995/04-)
日本分子生物学会(1993/04-)
日本免疫学会(1993/04-)

︎Show all ︎Show first 5

Research Interests 11

Immune checkpoint
Inhibitory receptor
Immunotherapy
Immunoregulation
Fc receptor
LILRB
Fc受容体
免疫療法
免疫制御
抑制受容体
immunoglobulin-like receptor

Research Areas 2

Life sciences / Immunology / immunology
Life sciences / Medical biochemistry / medical chemistry

Awards 3

科学技術分野の文部科学大臣表彰科学技術賞研究部門

2012/04　文部科学省　「免疫制御Fc受容体の研究」
平成16年度免疫学会賞

2004/12　日本免疫学会　「イムノグロブリン様受容体による免疫制御と免疫疾患に関する研究」
岡山工学振興会科学技術賞

1994/07　岡山工学振興会　「遺伝子ノックアウトを用いたマウス局所免疫系におけるFc受容体の機能解析」

Papers 276

TLR7/8 stress response drives histiocytosis in SLC29A3 disorders Peer-reviewed

Takuma Shibata, Ryota Sato, Masato Taoka, Shin-Ichiroh Saitoh, Mayumi Komine, Kiyoshi Yamaguchi, Susumu Goyama, Yuji Motoi, Jiro Kitaura, Kumi Izawa, Yoshio Yamauchi, Yumiko Tsukamoto, Takeshi Ichinohe, Etsuko Fujita, Ryosuke Hiranuma, Ryutaro Fukui, Yoichi Furukawa, Toshio Kitamura, Toshiyuki Takai, Arinobu Tojo, Mamitaro Ohtsuki, Umeharu Ohto, Toshiyuki Shimizu, Manabu Ozawa, Nobuaki Yoshida, Toshiaki Isobe, Eicke Latz, Kojiro Mukai, Tomohiko Taguchi, Hiroaki Hemmi, Shizuo Akira, Kensuke Miyake

Journal of Experimental Medicine　220　(9)　2023/07/18
Publisher: Rockefeller University Press
DOI： 10.1084/jem.20230054 　

ISSN： 0022-1007

eISSN： 1540-9538

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Loss-of-function mutations in the lysosomal nucleoside transporter SLC29A3 cause lysosomal nucleoside storage and histiocytosis: phagocyte accumulation in multiple organs. However, little is known about the mechanism by which lysosomal nucleoside storage drives histiocytosis. Herein, histiocytosis in Slc29a3−/− mice was shown to depend on Toll-like receptor 7 (TLR7), which senses a combination of nucleosides and oligoribonucleotides (ORNs). TLR7 increased phagocyte numbers by driving the proliferation of Ly6Chi immature monocytes and their maturation into Ly6Clow phagocytes in Slc29a3−/− mice. Downstream of TLR7, FcRγ and DAP10 were required for monocyte proliferation. Histiocytosis is accompanied by inflammation in SLC29A3 disorders. However, TLR7 in nucleoside-laden splenic monocytes failed to activate inflammatory responses. Enhanced production of proinflammatory cytokines was observed only after stimulation with ssRNAs, which would increase lysosomal ORNs. Patient-derived monocytes harboring the G208R SLC29A3 mutation showed enhanced survival and proliferation in a TLR8-antagonist-sensitive manner. These results demonstrated that TLR7/8 responses to lysosomal nucleoside stress drive SLC29A3 disorders.
Prognostic impact of LILRB4 expression on tumor‐infiltrating cells in resected non‐small cell lung cancer Peer-reviewed

Sakiko Kumata, Hirotsugu Notsuda, Mei‐Tzu Su, Ryoko Saito‐Koyama, Ryota Tanaka, Yuyo Suzuki, Junichi Funahashi, Shota Endo, Isao Yokota, Toshiyuki Takai, Yoshinori Okada

Thoracic Cancer　2023/06/08
Publisher: Wiley
DOI： 10.1111/1759-7714.14991 　

ISSN： 1759-7706

eISSN： 1759-7714
Fibronectin on target cells attenuates natural cytotoxicity of NK cells via myeloid immune checkpoint ILT3/LILRB4/gp49B Peer-reviewed

Fumika Itagaki, Keita Nakatsuka, Haruka Sakai, Shota Endo, Mei-Tzu Su, Toshiyuki Takai

International Immunology　35　(7)　339-348　2023/04/21
Publisher: Oxford University Press (OUP)
DOI： 10.1093/intimm/dxad012 　

eISSN： 1460-2377

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Abstract Natural killer (NK) cells play pivotal roles in innate immunity as well as in anti-tumor responses via natural killing, while their activity is tightly regulated by cell-surface inhibitory receptors. Immunoglobulin-like transcript 3/leukocyte immunoglobulin-like receptor B4 (ILT3/LILRB4, also known as gp49B in mice) is an inhibitory receptor expressed on activated NK cells as well as myeloid-lineage cells. The common physiologic ligand of human LILRB4 and gp49B was identified very recently as fibronectin, particularly the N-terminal 30 kDa domain (FN30). We hypothesized that LILRB4 could bind fibronectin on target cells in trans together with integrins, classical fibronectin receptors, in cis and deliver an inhibitory signal in NK cells, leading to attenuated natural killing. Flow cytometric and confocal microscopic analyses of NK cell-surface gp49B and integrins suggested that these novel and classical fibronectin receptors, respectively, co-engage fibronectin immobilized on a culture plate. Biochemical analyses indicated that tyrosine phosphorylation of spleen tyrosine kinase was augmented in gp49B-deficient NK cells upon binding to the immobilized fibronectin. While surface fibronectin-poor YAC-1 cells were evenly sensitive as to natural killing of both gp49B-positive and -negative NK cells, the killing of fibronectin-rich Lewis lung carcinoma cells, but not the FN30-knockout cells, was augmented among gp49B-deficient NK cells. These results suggest that the natural cytotoxicity of NK cells is negatively regulated through LILRB4/gp49B sensing fibronectin on target cells, which sheds light on the unexpected role of LILRB4 and fibronectin as a potential attenuator of NK cell cytotoxicity in the tumor microenvironment.
INPP5D modulates TREM2 loss-of-function phenotypes in a β-amyloidosis mouse model Peer-reviewed

Akihiro Iguchi, Sho Takatori, Shingo Kimura, Hiroki Muneto, Kai Wang, Hayato Etani, Genta Ito, Haruaki Sato, Yukiko Hori, Junko Sasaki, Takashi Saito, Takaomi C. Saido, Tsuneya Ikezu, Toshiyuki Takai, Takehiko Sasaki, Taisuke Tomita

iScience　26　(4)　106375-106375　2023/04
Publisher: Elsevier BV
DOI： 10.1016/j.isci.2023.106375 　

ISSN： 2589-0042
LILRB4/gp49B Co-Localizes with Integrin via Fibronectin at Focal Adhesion Sites on Mast Cells Peer-reviewed

Shotaro Miyamoto, Takumi Chiba, So Itoi, Mei-Tzu Su, Toshiyuki Takai

The Tohoku Journal of Experimental Medicine　259　(4)　273-284　2023
Publisher: Tohoku University Medical Press
DOI： 10.1620/tjem.2023.j001 　

ISSN： 0040-8727

eISSN： 1349-3329
Fibronectin-LILRB4/gp49B interaction negatively regulates osteoclastogenesis through inhibition of RANKL-induced TRAF6/TAK1/NF-kB/MAPK signaling. International-journal Peer-reviewed

Mei-Tzu Su, Karin Ono, Dai Kezuka, Shotaro Miyamoto, Yu Mori, Toshiyuki Takai

International immunology　2022/11/04

DOI： 10.1093/intimm/dxac051 　

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Dysregulation of osteoclasts, the multinucleated cells responsible for bone resorption, contributes to several degenerative bone disorders. Previously, we showed that blocking the leukocyte immunoglobulin (Ig)-like receptor B4 (LILRB4), a kind of inhibitory receptor that plays an important role in immune regulation, promotes osteoclast differentiation in vitro. Here, we explored whether gp49B, the murine ortholog of LILRB4, regulates osteoclastogenesis in vivo, and whether fibronectin (FN), a ligand of LILRB4/gp49B, certainly contributes to LILRB4/gp49B-mediated osteoclastogenesis. In comparison with wild-type mice, gp49B deficiency mice exhibited a loss of trabecular bone number and an increase in osteoclast formation. Gp49B knockout improved the bone resorptive capacity of osteoclasts derived from murine Raw264.7 cells by increasing osteoclast formation. We further revealed that gp49B deficiency increased the receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced signaling transduction by increasing the phosphorylation of TGF-activated kinase 1 (TAK1), NF-κB and mitogen-activated protein kinases (MAPKs). Furthermore, the N-terminal 30 kDa proteolytic fragments of FN promoted gp49B-mediated inhibition of osteoclastogenesis by increasing Src homology-2-containing tyrosine phosphatase 1 (SHP-1) phosphorylation and tumor necrosis factor receptor-associated factor 6 (TRAF6)-SHP-1 association. In summary, the FN-LILRB4/gp49B interaction negatively regulates RANKL-induced TRAF6/TAK1/NF-𝜅B/MAPK signaling in osteoclastogenesis.
Myeloid immune checkpoint ILT3/LILRB4/gp49B can co-tether fibronectin with integrin on macrophages. International-journal Peer-reviewed

So Itoi, Naoyuki Takahashi, Haruka Saito, Yusuke Miyata, Mei-Tzu Su, Dai Kezuka, Fumika Itagaki, Shota Endo, Hiroshi Fujii, Hideo Harigae, Yuzuru Sakamoto, Toshiyuki Takai

International immunology　34　(8)　435-444　2022/06/11

DOI： 10.1093/intimm/dxac023 　

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LILRB4 (B4, also known as ILT3/CD85k) is an immune checkpoint of myeloid-lineage cells, albeit its mode of function remains obscure. Our recent identification of a common ligand for both human B4 and its murine ortholog gp49B as the fibronectin (FN) N-terminal 30-kDa domain poses the question of how B4/gp49B regulate cellular activity upon recognition of FN in the plasma and/or the extracellular matrix. Since FN in the extracellular matrix is tethered by FN-binding integrins, we hypothesized that B4/gp49B would tether FN in cooperation with integrins on the cell surface, thus they should be in close vicinity to integrins spatially. This scenario suggests a mode of function of B4/gp49B by which the FN-induced signal is regulated. FN pull-down complex was found to contain gp49B and integrin β1 in bone marrow-derived macrophages. The confocal fluorescent signals of the three molecules on the intrinsically FN-tethering macrophages were correlated to each other. When FN-poor macrophages adhered to culture plate, the gp49-integrin β1 signal correlation increased at the focal adhesion, supporting the notion that gp49B and integrin β1 become spatially closer to each other there. While adherence of RAW264.7 and THP-1 cells to immobilized FN induced phosphorylation of spleen tyrosine kinase, whose level was augmented under B4/gp49B deficiency. Thus, we concluded that B4/gp49B can co-tether fibronectin in cooperation with integrin in the cis configuration on the same cell, forming a B4/gp49B-FN-integrin triplet as a regulatory unit of focal adhesion-dependent proinflammatory signal in macrophages.
Co-localization of Fibronectin Receptors LILRB4/gp49B and Integrin on Dendritic Cell Surface Peer-reviewed

Naoyuki Takahashi, So Itoi, Mei-Tzu Su, Shota Endo, Toshiyuki Takai

The Tohoku Journal of Experimental Medicine　257　(3)　171-180　2022
Publisher: Tohoku University Medical Press
DOI： 10.1620/tjem.2022.j014 　

ISSN： 0040-8727

eISSN： 1349-3329
LILRB4 promotes tumor metastasis by regulating MDSCs and inhibiting miR-1 family miRNAs. International-journal Peer-reviewed

Mei-Tzu Su, Sakiko Kumata, Shota Endo, Yoshinori Okada, Toshiyuki Takai

Oncoimmunology　11　(1)　2060907-2060907　2022
Publisher: Informa UK Limited
DOI： 10.1080/2162402X.2022.2060907 　

eISSN： 2162-402X

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Myeloid-derived suppressor cells (MDSCs) are a population of immune suppressive cells that are involved in tumor-associated immunosuppression, and dominate tumor progression and metastasis. In this study, we report that the leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4, murine ortholog gp49B) orchestrates the polarization of MDSCs to exhibit pro-tumor phenotypes. We found that gp49B deficiency inhibited tumor metastases of cancer cells, and reduced tumor-infiltration of monocytic MDSCs (M-MDSCs) in tumor-bearing mice. Gp49B-/- MDSCs inhibited pro-tumor immune responses, such as activation of Treg cells, promotion of cancer cell migration, and stimulation of tumor angiogenesis. Treatment of wild-type tumor-bearing mice with gp49B-/- M-MDSCs reduced cancer metastasis. Furthermore, gp49B knockout affected plasma exosome composition in terms of increased miR-1 family microRNAs (miRNAs) expression, which correlates with the upregulation of gp49B-/- MDSC-derived anti-tumor miRNAs. Collectively, our findings reveal that LILRB4/gp49B promotes MDSC-mediated tumor metastasis by regulating the M2-polarization of MDSCs and suppressing the secretion of miR-1 family miRNAs, which facilitate tumor migration and invasion. Abbreviations CTLA-4: cytotoxic T-lymphocyte-associated protein-4; FBS: fetal bovine serum; G-MDSCs: granulocytic-MDSCs; GP49B: glycoprotein 49B; HE: hematoxylin-eosin; ICI: immune checkpoint inhibitor; ITIM: immunoreceptor tyrosine-based inhibition motif; LILRB4: leukocyte immunoglobulin-like receptor B4; M-CSF: macrophage colony stimulating factor; MDSC: myeloid-derived suppressor cell; M-MDSC: monocytic MDSC; MMP-9: metallopeptidase-9; mAb: monoclonal antibody; PBS: phosphate-buffered saline; PCR: polymerase chain reaction; PD-1: programmed death-1; PD-L1: programmed death ligand-1; PMN-MDSC: polymorphonuclear-MDSC; qRT-PCR: quantitative reverse transcription PCR; TAM: tumor associated macrophage; TME: tumor microenvironment; TMM: trimmed mean of M value; VEGFA: vascular endothelial growth factor A.
Upregulation of leukocyte immunoglobulin-like receptor B4 on interstitial macrophages in COPD; their possible protective role against emphysema formation. International-journal Peer-reviewed

Ayumi Mitsune, Mitsuhiro Yamada, Naoya Fujino, Tadahisa Numakura, Tomohiro Ichikawa, Ayumi Suzuki, Shuichiro Matsumoto, Yoshiya Mitsuhashi, Koji Itakura, Tomonori Makiguchi, Akira Koarai, Tsutomu Tamada, Shota Endo, Toshiyuki Takai, Yoshinori Okada, Satoshi Suzuki, Masakazu Ichinose, Hisatoshi Sugiura

Respiratory research　22　(1)　232-232　2021/08/23

DOI： 10.1186/s12931-021-01828-3 　

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BACKGROUND: Leukocyte immunoglobulin-like receptor B4 (LILRB4) is one of the inhibitory receptors in various types of immune cells including macrophages. Previous reports suggested that LILRB4 could be involved in a negative feedback system to prevent excessive inflammatory responses. However, its role has been unclear in chronic obstructive pulmonary disease (COPD), in which macrophages play a crucial role in the pathogenesis. In this study, we aimed to examine the changes of LILRB4 on macrophages both in the lung specimens of COPD patients and the lungs of a mouse emphysema model. We then tried to compare the differences in both inflammation and emphysematous changes of the model between wild-type and LILRB4-deficient mice in order to elucidate the role of LILRB4 in the pathogenesis of COPD. METHODS: We prepared single-cell suspensions of resected lung specimens of never-smokers (n = 21), non-COPD smokers (n = 16), and COPD patients (n = 14). The identification of LILRB4-expressing cells and the level of LILRB4 expression were evaluated by flow cytometry. We analyzed the relationships between the LILRB4 expression and clinical characteristics including respiratory function. In the experiments using an elastase-induced mouse model of emphysema, we also analyzed the LILRB4 expression on lung macrophages. We compared inflammatory cell accumulation and emphysematous changes induced by elastase instillation between wild-type and LILRB4-deficient mice. RESULTS: The levels of surface expression of LILRB4 are relatively high on monocyte linage cells including macrophages in the human lungs. The percentage of LILRB4+ cells in lung interstitial macrophages was increased in COPD patients compared to non-COPD smokers (p = 0.018) and correlated with the severity of emphysematous lesions detected by CT scan (rs = 0.559, p < 0.001), whereas the amount of smoking showed no correlation with LILRB4 expression. Increased LILRB4 on interstitial macrophages was also observed in elastase-treated mice (p = 0.008). LILRB4-deficient mice showed severer emphysematous lesions with increased MMP-12 expression in the model. CONCLUSIONS: LILRB4 on interstitial macrophages was upregulated both in human COPD lungs and in a mouse model of emphysema. This upregulated LILRB4 may have a protective effect against emphysema formation, possibly through decreasing MMP-12 expression in the lungs.
Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin ameliorates autoimmune disease in BXSB/Yaa mice Peer-reviewed

Mei-Tzu Su, Masanori Inui, Yi Li Wong, Maika Takahashi, Akiko Sugahara-Tobinai, Karin Ono, Shotaro Miyamoto, Keiichi Murakami, Ari Itoh-Nakadai, Dai Kezuka, So Itoi, Shota Endo, Kouyuki Hirayasu, Hisashi Arase, Toshiyuki Takai

International Immunology　33　(8)　447-458　2021/06/05
Publisher: Oxford University Press (OUP)
DOI： 10.1093/intimm/dxab028 　

eISSN： 1460-2377

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<title>Abstract</title> The extracellular matrix (ECM) is the basis for virtually all cellular processes and is also related to tumor metastasis. Fibronectin (FN), a major ECM macromolecule expressed by different cell types and also present in plasma, consists of multiple functional modules that bind to ECM-associated, plasma, and cell-surface proteins such as integrins and FN itself, thus ensuring its cell-adhesive and modulatory role. Here we show that FN constitutes an immune checkpoint. Thus, FN was identified as a physiological ligand for a tumor/leukemia/lymphoma- as well as autoimmune-associated checkpoint, ILT3/LILRB4 (B4, CD85k). Human B4 and the murine ortholog, gp49B, bound FN with sub-micromolar affinities as assessed by bio-layer interferometry. The major B4-binding site in FN was located at the N-terminal 30-kDa module (FN30), which is apart from the major integrin-binding site present at the middle of the molecule. Blockade of B4–FN binding such as with B4 antibodies or a recombinant FN30-Fc fusion protein paradoxically ameliorated autoimmune disease in lupus-prone BXSB/Yaa mice. The unexpected nature of the B4–FN checkpoint in autoimmunity is discussed, referring to its potential role in tumor immunity.
Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction International-journal Peer-reviewed

Hiroyuki Konishi, Takayuki Okamoto, Yuichiro Hara, Okiru Komine, Hiromi Tamada, Mitsuyo Maeda, Fumika Osako, Masaaki Kobayashi, Akira Nishiyama, Yosky Kataoka, Toshiyuki Takai, Nobuyuki Udagawa, Steffen Jung, Keiko Ozato, Tomohiko Tamura, Makoto Tsuda, Koji Yamanaka, Tomoo Ogi, Katsuaki Sato, Hiroshi Kiyama

EMBO J　39　(22)　e104464　2020/11

DOI： 10.15252/embj.2020104464 　

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Microglia are the principal phagocytes that clear cell debris in the central nervous system (CNS). This raises the question, which cells remove cell debris when microglial phagocytic activity is impaired. We addressed this question using Siglechdtr mice, which enable highly specific ablation of microglia. Non-microglial mononuclear phagocytes, such as CNS-associated macrophages and circulating inflammatory monocytes, did not clear microglial debris. Instead, astrocytes were activated, exhibited a pro-inflammatory gene expression profile, and extended their processes to engulf microglial debris. This astrocytic phagocytosis was also observed in Irf8-deficient mice, in which microglia were present but dysfunctional. RNA-seq demonstrated that even in a healthy CNS, astrocytes express TAM phagocytic receptors, which were the main astrocytic phagocytic receptors for cell debris in the above experiments, indicating that astrocytes stand by in case of microglial impairment. This compensatory mechanism may be important for the maintenance or prolongation of a healthy CNS.
Nogo receptor antagonist LOTUS exerts suppression on axonal growth‐inhibiting receptor PIR‐B International-journal Peer-reviewed

Yuji Kurihara, Toshiyuki Takai, Kohtaro Takei

Journal of Neurochemistry　155　(3)　285-299　2020/11
Publisher: Wiley
DOI： 10.1111/jnc.15013 　

ISSN： 0022-3042

eISSN： 1471-4159

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Damaged axons in the adult mammalian central nervous system have a restricted regenerative capacity mainly because of Nogo protein, which is a major myelin-associated axonal growth inhibitor with binding to both receptors of Nogo receptor-1 (NgR1) and paired immunoglobulin-like receptor (PIR)-B. Lateral olfactory tract usher substance (LOTUS) exerts complete suppression of NgR1-mediated axonal growth inhibition by antagonizing NgR1. However, the regulation of PIR-B functions in neurons remains unknown. In this study, protein-protein interactions analyses found that LOTUS binds to PIR-B and abolishes Nogo-binding to PIR-B completely. Reverse transcription-polymerase chain reaction and immunocytochemistry revealed that PIR-B is expressed in dorsal root ganglions (DRGs) from wild-type and Ngr1-deficient mice (male and female). In these DRG neurons, Nogo induced growth cone collapse and neurite outgrowth inhibition, but treatment with the soluble form of LOTUS completely suppressed them. Moreover, Nogo-induced growth cone collapse and neurite outgrowth inhibition in Ngr1-deficient DRG neurons were neutralized by PIR-B function-blocking antibodies, indicating that these Nogo-induced phenomena were mediated by PIR-B. Our data show that LOTUS negatively regulates a PIR-B function. LOTUS thus exerts an antagonistic action on both receptors of NgR1 and PIR-B. This may lead to an improvement in the defective regeneration of axons following injury.
Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model Peer-reviewed

Sachiko Ono, Gyohei Egawa, Takashi Nomura, Akihiko Kitoh, Teruki Dainichi, Atsushi Otsuka, Saeko Nakajima, Masayuki Amagai, Fumi Matsumoto, Mami Yamamoto, Yoshiaki Kubota, Toshiyuki Takai, Tetsuya Honda, Kenji Kabashima

Nature Communications　10　(1)　2019/12/01

DOI： 10.1038/s41467-019-12232-3 　

eISSN： 2041-1723
Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity International-journal Peer-reviewed

Horiguchi Haruki, Kadomatsu Tsuyoshi, Kurahashi Ryoma, Hara Chiaki, Miyata Keishi, Baba Masaya, Osumi Hironobu, Terada Kazutoyo, Araki Kimi, Takai Toshiyuki, Kamba Tomomi, Linehan W. Marston, Moroishi Toshiro, Oike Yuichi

GENES & DEVELOPMENT　33　(23-24)　1641-1656　2019/12/01

DOI： 10.1101/gad.329417.119 　

ISSN： 0890-9369
CTLA4‐Ig Directly Inhibits Osteoclastogenesis by Interfering With Intracellular Calcium Oscillations in Bone Marrow Macrophages International-journal Peer-reviewed

Hiroyuki Okada, Hiroshi Kajiya, Yasunori Omata, Takumi Matsumoto, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Yosuke Kaneko, Shinya Nakamura, Takuma Koyama, Shunichi Sudo, Masashi Shin, Fujio Okamoto, Hisato Watanabe, Naohiro Tachibana, Jun Hirose, Taku Saito, Toshiyuki Takai, Morio Matsumoto, Masaya Nakamura, Koji Okabe, Takeshi Miyamoto, Sakae Tanaka

Journal of Bone and Mineral Research　34　(9)　1744-1752　2019/09
Publisher: Wiley
DOI： 10.1002/jbmr.3754 　

ISSN： 0884-0431

eISSN： 1523-4681

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CTLA4-Ig (cytotoxic T-lymphocyte antigen 4-immunoglobulin; Abatacept) is a biologic drug for rheumatoid arthritis. CTLA4 binds to the CD80/86 complex of antigen-presenting cells and blocks the activation of T cells. Although previous reports showed that CTLA4-Ig directly inhibited osteoclast differentiation, the whole inhibitory mechanism of CTLA4-Ig for osteoclast differentiation is unclear. Bone marrow macrophages (BMMs) from WT mice were cultured with M-CSF and RANKL with or without the recombinant mouse chimera CTLA4-Ig. Intracellular calcium oscillations of BMMs with RANKL were detected by staining with calcium indicator fura-2 immediately after administration of CTLA4-Ig or after one day of treatment. Calcium oscillations were analyzed using Fc receptor gamma- (FcRγ-) deficient BMMs. CTLA4-Ig inhibited osteoclast differentiation and reduced the expression of the nuclear factor of activated T cells NFATc1 in BMMs in vitro. Calcium oscillations in BMMs were suppressed by CTLA4-Ig both immediately after administration and after one day of treatment. CTLA4-Ig did not affect osteoclastogenesis and did not cause remarkable changes in calcium oscillations in FcRγ-deficient BMMs. Finally, to analyze the effect of CTLA4-Ig in vivo, we used an LPS-induced osteolysis model. CTLA4-Ig suppressed LPS-induced bone resorption in WT mice, not in FcRγ-deficient mice. In conclusion, CTLA4-Ig inhibits intracellular calcium oscillations depending on FcRγ and downregulates NFATc1 expression in BMMs. © 2019 American Society for Bone and Mineral Research.
Gp49B is a pathogenic marker for auto-antibody-producing plasma cells in lupus-prone BXSB/Yaa mice. International-journal Peer-reviewed

Wong YL, Su MT, Sugahara-Tobinai A, Itoi S, Kezuka D, Endo S, Inui M, Takai T

International immunology　31　(6)　397-406　2019/05

DOI： 10.1093/intimm/dxz017 　

ISSN： 0953-8178

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AbstractImmune homeostasis is critically regulated by the balance between activating and inhibitory receptors expressed on various immune cells such as T and B lymphocytes, and myeloid cells. The inhibitory receptors play a fundamental role in the immune checkpoint pathway, thus maintaining peripheral tolerance. We recently found that expression of leukocyte immunoglobulin-like receptor (LILR)B4, an inhibitory member of the human LILR family, is augmented in auto-antibody-producing plasmablasts/plasma cells of systemic lupus erythematosus (SLE) patients. However, the mechanism behind the 'paradoxical' up-regulation of this inhibitory receptor upon pathogenic antibody-secreting cells is yet to be known. To this end, in this study, we examined if glycoprotein 49B (gp49B), the murine counterpart of human LILRB4, is also elevated in auto-antibody-producing cells in several SLE mouse models, and tried to clarify the underlying mechanism. We found that gp49B is expressed on plasma cells of lupus-prone models but not of healthy C57BL/6 mice, and the level was positively correlated to the anti-double-stranded DNA IgG titer in serum. Gp49B genetic deletion, however, did not abolish the serum auto-antibodies or fully ameliorate the lethal glomerulonephritis, indicating that gp49B is not the sole regulator of lupus but a pathogenic element in the disease. We conclude that the elevated expression of this inhibitory receptor on pathogenic plasma cells was also relevant upon the murine SLE model. The mechanism of gp49B underlying the disease progression in lupus-prone mice has been discussed.
Augmented ILT3/LILRB4 Expression of Peripheral Blood Antibody Secreting Cells in the Acute Phase of Kawasaki Disease. International-journal Peer-reviewed

Sugahara-Tobinai A, Inui M, Metoki T, Watanabe Y, Onuma R, Takai T, Kumaki S

The Pediatric infectious disease journal　38　(4)　431-438　2019/04

DOI： 10.1097/INF.0000000000002259 　

ISSN： 0891-3668

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BACKGROUND: Kawasaki disease (KD) is an acute, systemic vasculitis syndrome that occurs in children. The clinical symptoms and epidemiologic features of KD strongly suggest that KD is triggered by unidentified infectious agents in genetically predisposed patients. In addition, a number of studies have described the role of B cells in the development of KD. To obtain a mechanistic insight into the humoral immune response of B-lineage cells in KD patients, we examined peripheral blood antibody secreting cells (ASCs) and inhibitory immunoreceptors, immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LILR), on each B cell subpopulation. METHODS: Eighteen Japanese KD patients and thirteen healthy control subjects were recruited for this study. Their peripheral blood mononuclear cells were examined by flow cytometry for the number of CD19 B cells, the size of each B cell subset and the expression of the inhibitory isoforms of ILT/LILR on the B cell subset. RESULTS: The frequency of CD19CD27 ASCs was significantly increased in the acute phase of KD and reduced after high-dose intravenous immunoglobulin (IVIG) treatment. Interestingly, while ILT2/LILRB1 expression was ubiquitously observed on every B cell/ASCs subset and the level was not significantly different after IVIG, ILT3/LILRB4 (B4) was uniquely expressed on only ASCs, and its expression was significantly decreased after IVIG. CONCLUSIONS: In the acute phase of KD, the frequency of ASCs is high with augmented B4 expression, whereas it is lower with decreased B4 expression after IVIG. Further studies of B4 expression on ASCs in autoimmune and infectious diseases will be needed to confirm the significance of our findings.
Leukocyte mono-immunoglobulin-like receptor 8 (LMIR8)/CLM-6 is an FcRγ-coupled receptor selectively expressed in mouse tissue plasmacytoid dendritic cells Peer-reviewed

Ayako Kaitani, Kumi Izawa, Akie Maehara, Masamichi Isobe, Ayako Takamori, Toshihiro Matsukawa, Mariko Takahashi, Yoshinori Yamanishi, Toshihiko Oki, Hiromichi Yamada, Masakazu Nagamine, Shino Uchida, Koichiro Uchida, Tomoaki Ando, Keiko Maeda, Nobuhiro Nakano, Toshiaki Shimizu, Toshiyuki Takai, Hideoki Ogawa, Ko Okumura, Toshio Kitamura, Jiro Kitaura

Scientific Reports　8　(1)　2018/12/01

DOI： 10.1038/s41598-018-25646-8 　

ISSN： 2045-2322

eISSN： 2045-2322
Bone marrow PDGFRα+Sca-1+-enriched mesenchymal stem cells support survival of and antibody production by plasma cells in vitro through IL-6 Peer-reviewed

Atsuko Kayaba, Ari Itoh-Nakadai, Kunimichi Niibe, Matsuyuki Shirota, Ryo Funayama, Akiko Sugahara-Tobinai, Yi Li Wong, Masanori Inui, Keiko Nakayama, Toshiyuki Takai

International Immunology　30　(6)　241-253　2018/05/24

DOI： 10.1093/intimm/dxy018 　

ISSN： 1460-2377 0953-8178
The CD300e molecule in mice is an immune-activating receptor Peer-reviewed

Masamichi Isobe, Kumi Izawa, Masahiro Sugiuchi, Tamami Sakanishi, Ayako Kaitani, Ayako Takamori, Akie Maehara, Toshihiro Matsukawa, Mariko Takahashi, Yoshinori Yamanishi, Toshihiko Oki, Shino Uchida, Koichiro Uchida, Tomoaki Ando, Keiko Maeda, Nobuhiro Nakano, Hideo Yagita, Toshiyuki Takai, Hideoki Ogawa, Ko Okumura, Toshio Kitamura, Jiro Kitaura

Journal of Biological Chemistry　293　(10)　3793-3805　2018

DOI： 10.1074/jbc.RA117.000696 　

ISSN： 1083-351X 0021-9258

eISSN： 1083-351X
PIR-B repressed IL-6 secretion from mesenchymal stem cells regulating the immunoglobulin production of plasma cells Peer-reviewed

Atsuko Kayaba, Ari Itoh-Nakadai, Masanori Inui, Toshiyuki Takai

CYTOKINE　100　163-164　2017/12

ISSN： 1043-4666

eISSN： 1096-0023
Secretory leukocyte peptidase inhibitor (SLPI) is highly expressed in long-lived plasma cells Peer-reviewed

Ari Itoh-Nakadai, Atsuko Kayaba, Toshiyuki Takai

CYTOKINE　100　166-166　2017/12

ISSN： 1043-4666

eISSN： 1096-0023
Identification of Secretory Leukoprotease Inhibitor As an Endogenous Negative Regulator in Allergic Effector Cells Peer-reviewed

Shintaro Matsuba, Toshiki Yabe-Wada, Kazuya Takeda, Tetsuya Sato, Mikita Suyama, Toshiyuki Takai, Toshiaki Kikuchi, Toshihiro Nukiwa, Akira Nakamura

FRONTIERS IN IMMUNOLOGY　8　2017/11

DOI： 10.3389/fimmu.2017.01538 　

ISSN： 1664-3224
Introduction: Antibody-Mediated Therapy Special Issue Part 2 Peer-reviewed

Nakamura Akira, Tsumoto Kouhei, Takai Toshiyuki

INTERNATIONAL IMMUNOLOGY　29　(11)　487-489　2017/11

DOI： 10.1093/intimm/dxx069 　

ISSN： 0953-8178
Introduction: Antibody-Mediated Therapy Special Issue Peer-reviewed

Akira Nakamura, Kouhei Tsumoto, Toshiyuki Takai

INTERNATIONAL IMMUNOLOGY　29　(7)　301-302　2017/07

DOI： 10.1093/intimm/dxx046 　

ISSN： 0953-8178

eISSN： 1460-2377
PirB regulates asymmetries in hippocampal circuitry Peer-reviewed

Hikari Ukai, Aiko Kawahara, Keiko Hirayama, Matthew Julian Case, Shotaro Aino, Masahiro Miyabe, Ken Wakita, Ryohei Oogi, Michiyo Kasayuki, Shihomi Kawashima, Shunichi Sugimoto, Kanako Chikamatsu, Noritaka Nitta, Tsuneyuki Koga, Ryuichi Shigemoto, Toshiyuki Takai, Isao Ito

PLOS ONE　12　(6)　2017/06

DOI： 10.1371/journal.pone.0179377 　

ISSN： 1932-6203
SLE病原性B細胞を特徴付ける抑制性受容体分子の探索

高井俊行, 乾匡範

アレルギー　66　(1)　27-31　2017/02
Publisher: (一社)日本アレルギー学会
ISSN： 0021-4884

eISSN： 1347-7935
Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines Peer-reviewed

Masayuki Hayashi, Taiki Aoshi, Yasunari Haseda, Kouji Kobiyama, Edward Wijaya, Noriyuki Nakatsu, Yoshinobu Igarashi, Daron M. Standley, Hiroshi Yamada, Yoshikazu Honda-Okubo, Hiromitsu Hara, Takashi Saito, Toshiyuki Takai, Cevayir Coban, Nikolai Petrovsky, Ken J. Ishii

EBIOMEDICINE　15　127-136　2017/02

DOI： 10.1016/j.ebiom.2016.11.015 　

ISSN： 2352-3964
Exploring of immune inhibitory receptors that characterize pathogenic plasma cells in systemic lupus erythematosus Peer-reviewed

Toshiyuki Takai, Masanori Inui

Japanese Journal of Allergology　66　(1)　27-31　2017
Publisher: Japanese Society of Allergology
ISSN： 1347-7935 0021-4884
Tolerogenic immunoreceptor ILT3/LILRB4 paradoxically marks pathogenic auto-antibody-producing plasmablasts and plasma cells in non-treated SLE Peer-reviewed

Masanori Inui, Akiko Sugahara-Tobinai, Hiroshi Fujii, Ari Itoh-Nakadai, Hidehiro Fukuyama, Tomohiro Kurosaki, Tomonori Ishii, Hideo Harigae, Toshiyuki Takai

INTERNATIONAL IMMUNOLOGY　28　(12)　597-604　2016/12

DOI： 10.1093/intimm/dxw044 　

ISSN： 0953-8178

eISSN： 1460-2377
TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain Peer-reviewed

Masaaki Kobayashi, Hiroyuki Konishi, Akira Sayo, Toshiyuki Takai, Hiroshi Kiyama

JOURNAL OF NEUROSCIENCE　36　(43)　11138-11150　2016/10

DOI： 10.1523/JNEUROSCI.1238-16.2016 　

ISSN： 0270-6474
The immunosuppressive effect of domain-deleted dimer of HLA-G2 isoform in collagen-induced arthritis mice Peer-reviewed

Ami Takahashi, Kimiko Kuroki, Yuki Okabe, Yoshiyuki Kasai, Naoki Matsumoto, Chisato Yamada, Toshiyuki Takai, Toyoyuki Ose, Shigeyuki Kon, Tadashi Matsuda, Katsumi Maenaka

HUMAN IMMUNOLOGY　77　(9)　754-759　2016/09

DOI： 10.1016/j.humimm.2016.01.010 　

ISSN： 0198-8859

eISSN： 1879-1166
Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity Peer-reviewed

Masaki Yugami, Haruki Odagiri, Motoyoshi Endo, Hiroyasu Tsutsuki, Shigemoto Fujii, Tsuyoshi Kadomatsu, Tetsuro Masuda, Keishi Miyata, Kazutoyo Terada, Hironori Tanoue, Hitoshi Ito, Jun Morinaga, Haruki Horiguchi, Taichi Sugizaki, Takaaki Akaike, Tomomi Gotoh, Toshiyuki Takai, Tomohiro Sawa, Hiroshi Mizuta, Yuichi Oike

JOURNAL OF BIOLOGICAL CHEMISTRY　291　(36)　18843-18852　2016/09

DOI： 10.1074/jbc.M116.720870 　

ISSN： 0021-9258

eISSN： 1083-351X
A Histone Methyltransferase ESET Is Critical for T Cell Development Peer-reviewed

Shoichi Takikita, Ryunosuke Muro, Toshiyuki Takai, Takeshi Otsubo, Yuki I. Kawamura, Taeko Dohi, Hiroyo Oda, Masayuki Kitajima, Kenshiro Oshima, Masahira Hattori, Takaho A. Endo, Tetsuro Toyoda, John Weis, Yoichi Shinkai, Harumi Suzuki

JOURNAL OF IMMUNOLOGY　197　(6)　2269-2279　2016/09

DOI： 10.4049/jimmunol.1502486 　

ISSN： 0022-1767

eISSN： 1550-6606
好酸球、マスト細胞、好塩基球好酸球におけるSLPIの制御機構の解明

松葉慎太郎, 和田俊樹, 武田和也, 佐藤哲也, 須山幹太, 高井俊行, 中村晃

アレルギー　65　(4-5)　558-558　2016/05
Publisher: (一社)日本アレルギー学会
ISSN： 0021-4884

eISSN： 1347-7935
TLR signals posttranscriptionally regulate the cytokine trafficking mediator sortilin Peer-reviewed

Toshiki Yabe-Wada, Shintaro Matsuba, Kazuya Takeda, Tetsuya Sato, Mikita Suyama, Yasuyuki Ohkawa, Toshiyuki Takai, Haifeng Shi, Caroline C. Philpott, Akira Nakamura

SCIENTIFIC REPORTS　6　2016/05

DOI： 10.1038/srep26566 　

ISSN： 2045-2322
Mechanism of action of immunoglobulin: Sialylated IgG Peer-reviewed

Toshiyuki Takai

Kawasaki Disease: Current Understanding of the Mechanism and Evidence-Based Treatment　223-230　2016/01/01
Publisher: Springer Japan
DOI： 10.1007/978-4-431-56039-5_25 　
Augmentation of neuropathic pain by DAP12 mediated signal in microglia

H. Konishi, M. Kobayashi, T. Takai, H. Kiyama

GLIA　63　E337-E337　2015/08

ISSN： 0894-1491

eISSN： 1098-1136
Human CD43(+) B cells are closely related not only to memory B cells phenotypically but also to plasmablasts developmentally in healthy individuals Peer-reviewed

Masanori Inui, Saeko Hirota, Kumiko Hirano, Hiroshi Fujii, Akiko Sugahara-Tobinai, Tomonori Ishii, Hideo Harigae, Toshiyuki Takai

INTERNATIONAL IMMUNOLOGY　27　(7)　345-355　2015/07

DOI： 10.1093/intimm/dxv009 　

ISSN： 0953-8178

eISSN： 1460-2377
A DAP12-Dependent Signal Promotes Pro-Inflammatory Polarization in Microglia Following Nerve Injury and Exacerbates Degeneration of Injured Neurons Peer-reviewed

Masaaki Kobayashi, Hiroyuki Konishi, Toshiyuki Takai, Hiroshi Kiyama

GLIA　63　(6)　1073-1082　2015/06

DOI： 10.1002/glia.22802 　

ISSN： 0894-1491

eISSN： 1098-1136
Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses Peer-reviewed

Toshifumi Kimura, Shota Endo, Masanori Inui, Shin-Ichiroh Saitoh, Kensuke Miyake, Toshiyuki Takai

JOURNAL OF IMMUNOLOGY　194　(11)　5426-5436　2015/06

DOI： 10.4049/jimmunol.1402006 　

ISSN： 0022-1767

eISSN： 1550-6606
Impaired fracture healing caused by deficiency of the immunoreceptor adaptor protein DAP12 Peer-reviewed

Masayuki Kamimura, Yu Mori, Akiko Sugahara-Tobinai, Toshiyuki Takai, Eiji Itoi

PLoS ONE　10　(6)　2015/06/01

DOI： 10.1371/journal.pone.0128210 　

ISSN： 1932-6203

eISSN： 1932-6203
Platelets convert peripheral blood circulating monocytes to regulatory cells via immunoglobulin G and activating-type Fc gamma receptors Peer-reviewed

Masanori Inui, Kino Tazawa, Yoshiro Kishi, Toshiyuki Takai

BMC IMMUNOLOGY　16　2015/04

DOI： 10.1186/s12865-015-0086-z 　

ISSN： 1471-2172
Immune complexes regulate bone metabolism through FcR gamma signalling Peer-reviewed

Takako Negishi-Koga, Hans-Juergen Gober, Eriko Sumiya, Noriko Komatsu, Kazuo Okamoto, Shinichiro Sawa, Ayako Suematsu, Tomomi Suda, Kojiro Sato, Toshiyuki Takai, Hiroshi Takayanagi

NATURE COMMUNICATIONS　6　2015/03

DOI： 10.1038/ncomms7637 　

ISSN： 2041-1723
Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases Peer-reviewed

Atsuo Kanno, Natsuko Tanimura, Masayuki Ishizaki, Kentaro Ohko, Yuji Motoi, Masahiro Onji, Ryutaro Fukui, Takaichi Shimozato, Kazuhide Yamamoto, Takuma Shibata, Shigetoshi Sano, Akiko Sugahara-Tobinai, Toshiyuki Takai, Umeharu Ohto, Toshiyuki Shimizu, Shin-ichiroh Saitoh, Kensuke Miyake

NATURE COMMUNICATIONS　6　2015/02

DOI： 10.1038/ncomms7119 　

ISSN： 2041-1723
TREM-1 regulates macrophage polarization in ureteral obstruction Peer-reviewed

Tzu-Han Lo, Kai-Yu Tseng, Wen-Shan Tsao, Chih-Ya Yang, Shie-Liang Hsieh, Allen Wen-Hsiang Chiu, Toshiyuki Takai, Tak W. Mak, Der-Cherng Tarng, Nien-Jung Chen

KIDNEY INTERNATIONAL　86　(6)　1174-1186　2014/12

DOI： 10.1038/ki.2014.205 　

ISSN： 0085-2538

eISSN： 1523-1755
TLR9シグナルの新規制御分子Sortilinの機能解析

和田俊樹, 武田和也, 松葉慎太郎, 中村晃, 佐藤哲也, 須山幹太, 大川恭行, 高井俊行

金沢医科大学雑誌　39　(2)　45-45　2014/10
Publisher: 金沢医科大学医学会
ISSN： 0385-5759
Dichotomy in Fc gamma RIIB deficiency and autoimmune-prone SLAM haplotype clarifies the roles of the Fc receptor in development of autoantibodies and glomerulonephritis Peer-reviewed

Yasuyoshi Kanari, Akiko Sugahara-Tobinai, Haruka Takahashi, Masanori Inui, Akira Nakamura, Sachiko Hirose, Toshiyuki Takai

BMC IMMUNOLOGY　15　2014/10

DOI： 10.1186/s12865-014-0047-y 　

ISSN： 1471-2172
gp49B-Mediated Negative Regulation of Antibody Production by Memory and Marginal Zone B Cells Peer-reviewed

Saori Fukao, Kei Haniuda, Takuya Nojima, Toshiyuki Takai, Daisuke Kitamura

JOURNAL OF IMMUNOLOGY　193　(2)　635-644　2014/07

DOI： 10.4049/jimmunol.1302772 　

ISSN： 0022-1767

eISSN： 1550-6606
An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells Peer-reviewed

Shinsuke Yasukawa, Yoshiyuki Miyazaki, Chika Yoshii, Mako Nakaya, Naoko Ozaki, Shuji Toda, Etsushi Kuroda, Ken-ichi Ishibashi, Tomoharu Yasuda, Yohei Natsuaki, Fumika Mi-ichi, Ei'ichi Iizasa, Takeshi Nakahara, Masanori Yamazaki, Kenji Kabashima, Yoichiro Iwakura, Toshiyuki Takai, Takashi Saito, Tomohiro Kurosaki, Bernard Malissen, Naohito Ohno, Masutaka Furue, Hiroki Yoshida, Hiromitsu Hara

NATURE COMMUNICATIONS　5　2014/05

DOI： 10.1038/ncomms4755 　

ISSN： 2041-1723
Role of TREM1-DAP12 in renal inflammation during obstructive nephropathy Peer-reviewed

Alessandra Tammaro, Ingrid Stroo, Elena Rampanelli, Froilan Blank, Loes M. Butter, Nike Claessen, Toshiyuki Takai, Marco Colonna, Jaklien C. Leemans, Sandrine Florquin, Mark C. Dessing

PLoS ONE　8　(12)　2013/12/16

DOI： 10.1371/journal.pone.0082498 　

ISSN： 1932-6203
Environmental factors determine DAP12 deficiency to either enhance or suppress immunopathogenic processes Peer-reviewed

Vanessa Montalvo, Laura Quigley, Barbara P. Vistica, Kimberly C. Boelte, Lindsey F. Nugent, Toshiyuki Takai, Daniel W. McVicar, Igal Gery

IMMUNOLOGY　140　(4)　475-482　2013/12

DOI： 10.1111/imm.12158 　

ISSN： 0019-2805

eISSN： 1365-2567
好塩基球・好酸球におけるSLPIの制御機構の解明

松葉慎太郎, 和田俊樹, 武田和也, 佐藤哲也, 須山幹太, 高井俊行, 中村晃

アレルギー　62　(9-10)　1407-1407　2013/10
Publisher: (一社)日本アレルギー学会
ISSN： 0021-4884

eISSN： 1347-7935
IgG and IgE collaboratively accelerate expulsion of Strongyloides venezuelensis in a primary infection Peer-reviewed

Makoto Matsumoto, Yuki Sasaki, Koubun Yasuda, Toshiyuki Takai, Masamichi Muramatsu, Tomohiro Yoshimoto, Kenji Nakanishi

Infection and Immunity　81　(7)　2518-2527　2013/07

DOI： 10.1128/IAI.00285-13 　

ISSN： 0019-9567 1098-5522
Fc gamma RIIb mediates amyloid-beta neurotoxicity and memory impairment in Alzheimer's disease Peer-reviewed

Tae-In Kam, Sungmin Song, Youngdae Gwon, Hyejin Park, Ji-Jing Yan, Isak Im, Ji-Woo Choi, Tae-Yong Choi, Jeongyeon Kim, Dong-Keun Song, Toshiyuki Takai, Yong-Chul Kim, Key-Sun Kim, Se-Young Choi, Sukwoo Choi, William L. Klein, Junying Yuan, Yong-Keun Jung

JOURNAL OF CLINICAL INVESTIGATION　123　(7)　2791-2802　2013/07

DOI： 10.1172/JCI66827 　

ISSN： 0021-9738
【免疫グロブリン様受容体による免疫制御と疾患】自己免疫病とPirB

乾匡範, 高井俊行

医学のあゆみ　245　(3)　225-228　2013/04
Publisher: 医歯薬出版(株)
ISSN： 0039-2359
Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Yaa mutation into Fc gamma RIIB-deficient C57BL/6 mice Peer-reviewed

Kawano Shinya, Lin Qingshun, Amano Hirofumi, Kaneko Toshiyuki, Nishikawa Keiko, Tsurui Hiromichi, Tada Norihiro, Nishimura Hiroyuki, Takai Toshiyuki, Shirai Toshikazu, Takasaki Yoshinari, Hirose Sachiko

EUROPEAN JOURNAL OF IMMUNOLOGY　43　(3)　770-778　2013/03

DOI： 10.1002/eji.201243057 　

ISSN： 0014-2980
Inhibitory Receptor Paired Ig-like Receptor B Is Exploited by Staphylococcus aureus for Virulence International-journal Peer-reviewed

Nakayama Masafumi, Kurokawa Kenji, Nakamura Kyohei, Lee Bok Luel, Sekimizu Kazuhisa, Kubagawa Hiromi, Hiramatsu Keiichi, Yagita Hideo, Okumura Ko, Takai Toshiyuki, Underhill David M, Aderem Alan, Ogasawara Kouetsu

JOURNAL OF IMMUNOLOGY　189　(12)　5903-5911　2012/12/15

DOI： 10.4049/jimmunol.1201940 　

ISSN： 0022-1767

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The innate immune system has developed to acquire a wide variety of pattern-recognition receptors (PRRs) to identify potential pathogens, whereas pathogens have also developed to escape host innate immune responses. ITIM-bearing receptors are attractive targets for pathogens to attenuate immune responses against them; however, the in vivo role of the inhibitory PRRs in host-bacteria interactions remains unknown. We demonstrate in this article that Staphylococcus aureus, a major Gram-positive bacteria, exploits inhibitory PRR paired Ig-like receptor (PIR)-B on macrophages to suppress ERK1/2 and inflammasome activation, and subsequent IL-6 and IL-1β secretion. Consequently, Pirb(-/-) mice infected with S. aureus showed enhanced inflammation and more effective bacterial clearance, resulting in resistance to the sepsis. Screening of S. aureus mutants identified lipoteichoic acid (LTA) as an essential bacterial cell wall component required for binding to PIR-B and modulating inflammatory responses. In vivo, however, an LTA-deficient S. aureus mutant was highly virulent and poorly recognized by macrophages in both wild-type and Pirb(-/-) mice, demonstrating that LTA recognition by PRRs other than PIR-B mediates effective bacterial elimination. These results provide direct evidence that bacteria exploit the inhibitory receptor for virulence, and host immune system counterbalances the infection.
The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis. Peer-reviewed

Kuroki K, Hirose K, Okabe Y, Fukunaga Y, Takahashi A, Shiroishi M, Kajikawa M, Tabata S, Nakamura S, Takai T, Koyanagi S, Ohdo S, Maenaka K

Human immunology　74　(4)　433-438　2012/12
Publisher: ELSEVIER SCIENCE INC
DOI： 10.1016/j.humimm.2012.11.060 　

ISSN： 0198-8859
【骨免疫学〜基礎と臨床〜】免疫グロブリン様受容体による破骨細胞の分化制御

乾匡範, 高井俊行

Clinical Calcium　22　(11)　1651-1657　2012/10
Publisher: (株)医薬ジャーナル社
ISSN： 0917-5857
Regulation of plasmacytoid dendritic cell responses by PIR-B. Peer-reviewed

Yoshiya Mitsuhashi, Akira Nakamura, Shota Endo, Kazuya Takeda, Toshiki Yabe-Wada, Toshihiro Nukiwa, Toshiyuki Takai

Blood　120　(16)　3256-3259　2012/09
Publisher: American Society of Hematology
DOI： 10.1182/blood-2012-03-419093 　

ISSN： 0006-4971

eISSN： 1528-0020

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<title>Abstract</title> Plasmacytoid dendritic cells (PDCs) produce type I interferons (IFNs) in response to viral nucleic acids to exert antiviral immunity. However, PDCs are related to the progress and severity of autoimmune diseases, such as systemic lupus erythematosus, because they respond to host DNA. Therefore, the regulation of PDC activation is critical for maintaining adequate immune responses. Here we show that an inhibitory major histocompatibility complex class I receptor, paired immunoglobulin-like receptor B (PIR-B), suppressed Fms-like tyrosine kinase 3 ligand-induced PDC differentiation in BM cells, as well as Toll-like receptor 9-mediated IFN-α production by PDCs, through the dephosphorylation of STAT1/STAT2. In particular, PIR-B inhibited IFN-α–mediated STAT phosphorylation, suggesting that PIR-B negatively regulates the positive feedback mechanism of IFN-α secretion triggered by Toll-like receptor 9. These results demonstrate a novel regulatory role for PIR-B in PDCs.
Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7 Peer-reviewed

Lior Zangi, Yael Zlotnikov Klionsky, Liran Yarimi, Esther Bachar-Lustig, Yaki Eidelstein, Elias Shezen, David Hagin, Yumi Ito, Toshiyuki Takai, Shlomit Reich-Zeliger, Assaf Lask, Oren Milstein, Steffen Jung, Vera Shinder, Yair Reisner

BLOOD　120　(8)　1647-1657　2012/08

DOI： 10.1182/blood-2012-02-410803 　

ISSN： 0006-4971
Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells. Peer-reviewed

Wong WF, Kohu K, Nakamura A, Ebina M, Kikuchi T, Tazawa R, Tanaka K, Kon S, Funaki T, Sugahara-Tobinai A, Looi CY, Endo S, Funayama R, Kurokawa M, Habu S, Ishii N, Fukumoto M, Nakata K, Takai T, Satake M

Journal of immunology (Baltimore, Md. : 1950)　188　5408-5420　2012/06
Publisher: 11
DOI： 10.4049/jimmunol.1102991 　

ISSN： 0022-1767
【骨吸収の正と負の制御】破骨細胞共刺激受容体による正と負の制御

乾匡範, 高井俊行

炎症と免疫　20　(3)　240-245　2012/04
Publisher: (株)先端医学社
ISSN： 0918-8371
Intravenous immunoglobulin suppresses IL-10 production by activated B cells in vitro Peer-reviewed

Jun Tanaka, Kumiko Hirano, Yuzuru Sakamoto, Akiko Sugahara-Tobinai, Shota Endo, Yumi Ito-Matsuoka, Atsushi Nakano, Masanori Inui, Lars Nitschke, Toshiyuki Takai

Open Journal of Immunology　02　(04)　149-160　2012
Publisher: Scientific Research Publishing, Inc.
DOI： 10.4236/oji.2012.24019 　

ISSN： 2162-450X

eISSN： 2162-4526
Control of Pathogenic CD4 T Cells and Lethal Immunopathology by Signaling Immunoadaptor DAP12 during Influenza Infection Peer-reviewed

Sarah McCormick, Christopher R. Shaler, Cherrie-Lee Small, Carly Horvath, Daniela Damjanovic, Earl G. Brown, Naoko Aoki, Toshiyuki Takai, Zhou Xing

JOURNAL OF IMMUNOLOGY　187　(8)　4280-4292　2011/10

DOI： 10.4049/jimmunol.1101050 　

ISSN： 0022-1767
Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+ CD11c+ cells. Peer-reviewed

Daito H, Kikuchi T, Sakakibara T, Gomi K, Damayanti T, Zaini J, Tode N, Kanehira M, Koyama S, Fujimura S, Ebina M, Ishii KJ, Akira S, Takai T, Watanabe A, Nukiwa T

The European respiratory journal　38　688-701　2011/09
Publisher: 3
DOI： 10.1183/09031936.00177110 　

ISSN： 0903-1936
The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses Peer-reviewed

Nakano-Yokomizo, Takako, Tahara-Hanaoka, Satoko, Nakahashi-Oda, Chigusa, Nabekura, Tsukasa, Tchao, Nadia K, Kadosaki, Momoko, Totsuka, Naoya, Kurita, Naoki, Nakamagoe, Kiyotaka, Tamaoka, Akira, Takai, Toshiyuki, Yasui, Teruhito, Kikutani, Hitoshi, Honda, Shin-ichiro, Shibuya, Kazuko, Lanier, Lewis L, Shibuya, Akira

JOURNAL OF EXPERIMENTAL MEDICINE　208　(8)　1661-1671　2011/08
Publisher: ROCKEFELLER UNIV PRESS
DOI： 10.1084/jem.20101623 　

ISSN： 0022-1007

eISSN： 1540-9538
Differential but competitive binding of Nogo protein and class i major histocompatibility complex (MHCI) to the PIR-B ectodomain provides an inhibition of cells. Peer-reviewed

Matsushita H, Endo S, Kobayashi E, Sakamoto Y, Kobayashi K, Kitaguchi K, Kuroki K, Söderhäll A, Maenaka K, Nakamura A, Strittmatter SM, Takai T

The Journal of biological chemistry　286　(29)　25739-25747　2011/07

DOI： 10.1074/jbc.M110.157859 　

ISSN： 0021-9258
Transcriptional activation of the Pirb gene in B cells by PU.1 and Runx3. Peer-reviewed

Arita K, Endo S, Kaifu T, Kitaguchi K, Nakamura A, Ohmori H, Kohu K, Satake M, Takai T

Journal of immunology (Baltimore, Md. : 1950)　186　(12)　7050-7059　2011/06

DOI： 10.4049/jimmunol.1001302 　

ISSN： 0022-1767
Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity. Peer-reviewed

Fujita Y, Endo S, Takai T, Yamashita T

The EMBO journal　30　(7)　1389-1401　2011/04

DOI： 10.1038/emboj.2011.55 　

ISSN： 0261-4189
Paired immunoglobin-like receptor-B regulates the suppressive function and fate of myeloid-derived suppressor cells Peer-reviewed

Ge Ma, Ping-Ying Pan, Samuel Eisenstein, Celia M. Divino, Clifford A. Lowell, Toshiyuki Takai, Shu-Hsia Chen

Immunity　34　(3)　385-395　2011/03/25

DOI： 10.1016/j.immuni.2011.02.004 　

ISSN： 1074-7613 1097-4180
Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury. International-journal Peer-reviewed

Nakamura Y, Fujita Y, Ueno M, Takai T, Yamashita T

The Journal of biological chemistry　286　(3)　1876-1883　2011/01/02
Publisher: 3
DOI： 10.1074/jbc.M110.163493 　

ISSN： 0021-9258

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Myelin components that inhibit axonal regeneration are believed to contribute significantly to the lack of axonal regeneration noted in the adult central nervous system. Three proteins found in myelin, Nogo, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein, inhibit neurite outgrowth in vitro. All of these proteins interact with the same receptors, namely, the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PIR-B). As per previous reports, corticospinal tract (CST) regeneration is not enhanced in NgR-knock-out mice after spinal cord injury. Therefore, we assessed CST regeneration in PIR-B-knock-out mice. We found that hindlimb motor function, as assessed using the Basso mouse scale, footprint test, inclined plane test, and beam walking test, did not differ between the PIR-B-knock-out and wild-type mice after dorsal hemisection of the spinal cord. Further, tracing of the CST fibers after injury did not reveal enhanced axonal regeneration or sprouting in the CST of the PIR-B-knock-out mice. Systemic administration of NEP1-40, a NgR antagonist, to PIR-B knock-out mice did not enhance the regenerative response. These results indicate that PIR-B knock-out is not sufficient to induce extensive axonal regeneration after spinal cord injury.
S12-3 NogoおよびMHC class IによるPIR-Bを介した新たなマスト細胞の制御機構(S12 アレルギー治療標的としてのシグナル受容体,シンポジウム,第61回日本アレルギー学会秋季学術大会)

乾匡範, 篠崎夏子, 遠藤章太, 高井俊行

アレルギー　60　(9)　1232-1232　2011
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.60.1232_2 　
MS16-6 NogoおよびMHCクラスIによるPIR-Bへの競合的結合によるマスト細胞の制御について(MS16 マスト細胞2,ミニシンポジウム,第61回日本アレルギー学会秋季学術大会)

篠崎夏子, 乾匡範, 遠藤章太, 坂本譲, 北口公司, 高井俊行

アレルギー　60　(9)　1346-1346　2011
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.60.1346_3 　
Preparation of magnetite aqueous dispersion for magnetic fluid hyperthermia. Peer-reviewed

Teppei Kikuchi, Ryo Kasuya, Shota Endo, Akira Nakamura, Toshiyuki Takai, Nils Metzler-Nolte, Kazuyuki Tohji, Jeyadevan Balachandran

Journal of Magnetism and Magnetic Materials　323　1216-1222　2011

DOI： 10.1016/j.jmmm.2010.11.009 　
The p75 receptor mediates axon growth inhibition through an association with PIR-B. Peer-reviewed

Yuki Fujita, Reina Takashima, Shota Endo, Toshiyuki Takai, Toshihide Yamashita

Cell Death & Disease　2　e198　2011

DOI： 10.1038/cddis.2011.85 　
Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells. Peer-reviewed

Proc. Natl. Acad. Sci. USA.　108　(45)　18360-18365　2011

DOI： 10.1073/pnas.1110584108 　

ISSN： 0027-8424
Role of PIR-B in Autoimmune Glomerulonephritis Peer-reviewed

Toshiyuki Takai, Akira Nakamura, Shota Endo

JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY　2011　275302-275302　2011

DOI： 10.1155/2011/275302 　

ISSN： 1110-7243
The inhibitory effects of intravenous administration of rabbit immunoglobulin G on airway inflammation are dependent upon Fcγ receptor IIb on CD11c(+) dendritic cells in a murine model. International-journal

M Yamamoto, K Kobayashi, Y Ishikawa, K Nakata, Y Funada, Y Kotani, A Masuda, T Takai, T Azuma, M Yoshida, Y Nishimura

Clinical and experimental immunology　162　(2)　315-24　2010/11

DOI： 10.1111/j.1365-2249.2010.04243.x 　

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Immunoglobulins (Igs) play important immunomodulatory effects on allergic asthma. Among these, IgG has been reported to regulate allergic inflammation in previous studies about immunotherapy and intravenous immunoglobulin therapy. In this study, to examine the immunomodulatory mechanisms of IgG and FcRs we evaluated the effects of intravenous (i.v.) rabbit IgG administration (IVIgG) on allergic airway inflammation and lung antigen-presenting cells (APCs) in a murine model of ovalbumin (OVA) sensitization and challenge. In OVA-challenged mice, IVIgG attenuated airway eosinophilia, airway hyperresponsiveness and goblet cell hyperplasia and also inhibited the local T helper type (Th) 2 cytokine levels. Additionally, IVIgG attenuated the proliferation of OVA-specific CD4(+) T cells transplanted into OVA-challenged mice. Ex vivo co-culture with OVA-specific CD4(+) cells and lung CD11c(+) APCs from mice with IVIgG revealed the attenuated transcription level of Th2 cytokines, suggesting an inhibitory effect of IVIgG on CD11c(+) APCs to induce Th2 response. Next, to analyse the effects on Fcγ receptor IIb and dendritic cells (DCs), asthmatic features in Fcγ receptor IIb-deficient mice were analysed. IVIgG failed to attenuate airway eosinophilia, airway inflammation and goblet cell hyperplasia. However, the lacking effects of IVIgG on airway eosinophilia in Fcγ receptor IIb deficiency were restored by i.v. transplantation of wild-type bone marrow-derived CD11c(+) DCs. These results demonstrate that IVIgG attenuates asthmatic features and the function of lung CD11c(+) DCs via Fcγ receptor IIb in allergic airway inflammation. Targeting Fc portions of IgG and Fcγ receptor IIb on CD11c(+) DCs in allergic asthma is a promising therapeutic strategy.
Characterization of Leukocyte Mono-immunoglobulin-like Receptor 7 (LMIR7)/CLM-3 as an Activating Receptor ITS SIMILARITIES TO AND DIFFERENCES FROM LMIR4/CLM-5 Peer-reviewed

Yutaka Enomoto, Yoshinori Yamanishi, Kumi Izawa, Ayako Kaitani, Mariko Takahashi, Akie Maehara, Toshihiko Oki, Reiko Takamatsu, Masunori Kajikawa, Toshiyuki Takai, Toshio Kitamura, Jiro Kitaura

JOURNAL OF BIOLOGICAL CHEMISTRY　285　(46)　35274-35283　2010/11

DOI： 10.1074/jbc.M110.137166 　

ISSN： 0021-9258

eISSN： 1083-351X
Genetic Deletion of Paired Immunoglobulin-Like Receptor B Does Not Promote Axonal Plasticity or Functional Recovery after Traumatic Brain Injury Peer-reviewed

Shusaku Omoto, Masaki Ueno, Soichiro Mochio, Toshiyuki Takai, Toshihide Yamashita

JOURNAL OF NEUROSCIENCE　30　(39)　13045-13052　2010/09

DOI： 10.1523/JNEUROSCI.3228-10.2010 　

ISSN： 0270-6474
Paired immunoglobulin-like receptor B(PirB)ノックアウトマウスにおける外傷性脳損傷後の運動機能回復および神経可塑性(Genetic deletion of paired immunoglobulin-like receptor B does not promote axonal plasticity or functional recovery after traumatic brain injury)

大本周作, 上野将紀, 持尾聰一郎, 高井俊行, 山下俊英

神経化学　49　(2-3)　628-628　2010/08
Publisher: 日本神経化学会
ISSN： 0037-3796
TIM1 is an endogenous ligand for LMIR5/CD300b: LMIR5 deficiency ameliorates mouse kidney ischemia/reperfusion injury Peer-reviewed

Yoshinori Yamanishi, Jiro Kitaura, Kumi Izawa, Ayako Kaitani, Yukiko Komeno, Masaki Nakamura, Satoshi Yamazaki, Yutaka Enomoto, Toshihiko Oki, Hisaya Akiba, Takaya Abe, Tadasuke Komori, Yoshihiro Morikawa, Hiroshi Kiyonari, Toshiyuki Takai, Ko Okumura, Toshio Kitamura

JOURNAL OF EXPERIMENTAL MEDICINE　207　(7)　1501-1511　2010/07

DOI： 10.1084/jem.20090581 　

ISSN： 0022-1007
Heat dissipation characteristics of magnetite nanoparticles and their application to macrophage cells Peer-reviewed

Ryo Kasuya, Teppei Kikuchi, Hiroaki Mamiya, Koji Ioku, Shota Endo, Akira Nakamura, Toshiyuki Takai, Jeyadevan Balachandran

Physics Procedia　9　186-189　2010

DOI： 10.1016/j.phpro.2010.11.042 　

ISSN： 1875-3892
NKT細胞とその他の自然リンパ球基礎的解析 TIM1とTIM4はLMIR5/CD300bのリガンドである TIM1/4-LMIR5相互作用による肥満細胞と顆粒球におけるLMIR5介在性活性化の誘導(TIM1 and TIM4 are ligands for LMIR5/CD300b: the TIM1/4-LMIR5 interaction induces LMIR5-mediated activation of mast cells and granulocytes)

Yamanishi Yoshinori, Kitaura Jiro, Izawa Kumi, Kaitani Ayako, Enomoto Yutaka, Oki Toshihiko, Akiba Hisaya, Takai Toshiyuki, Okumura Ko, Kitamura Toshio

日本免疫学会総会・学術集会記録　39　59-59　2009/11
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
【骨免疫学】RANK共刺激受容体による骨代謝の制御

乾匡範, 菊地佑樹, 高井俊行

THE BONE　23　(4)　409-414　2009/10
Publisher: (株)メディカルレビュー社
ISSN： 0914-7047
Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses. International-journal Peer-reviewed

Michiyo Imada, Kyoko Masuda, Rumi Satoh, Yumi Ito, Yoshiyuki Goto, Takayuki Matsuoka, Shota Endo, Akira Nakamura, Hiroshi Kawamoto, Toshiyuki Takai

International immunology　21　(10)　1151-61　2009/10

DOI： 10.1093/intimm/dxp081 　

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Activated mature T cells induce various inhibitory receptors implicated in maintaining peripheral tolerance in response to the trans-acting ligands. Interestingly, paired Ig-like receptor (PIR)-B, an inhibitory MHC class I receptor on B cells and myeloid cells, could be involved in regulating early T cell development because epitope for PIR is detected on pre-thymic T/NK progenitors but not on thymocytes or mature T cells. We hypothesized that PIR-B is not only a regulator for T cell development but is also detrimental if expressed on mature T cells. Here we demonstrated, using PIR-B-deficient fetuses, that PIR-B is indeed expressed on the T cell progenitors but failed to identify its distinctive roles in the development. Forced expression of PIR-B in thymocytes and mature T cells also resulted in no abnormalities in development. However, upon antigenic or allogeneic stimulation, peripheral T cells with the ectopic PIR-B showed reduced T(h) type 1 responses due to the suppression of proximal TCR signaling by constitutive binding of PIR-B to MHC class I on the same cell surface. Our findings suggest that T cell expression of PIR-B with the cis-interacting MHC class I is strictly prohibited in periphery so as to secure prompt immune responses.
Autoimmune thyroiditis in Fc gamma receptor-deficient nonobese diabetic mice Peer-reviewed

Hiroshi Ozaki, Kouki Mori, Yoshinori Nakagawa, Saeko Hoshikawa, Sadayoshi Ito, Yoshihiro Inoue, Toshiyuki Takai, Katsumi Yoshida

CLINICAL IMMUNOLOGY　132　(2)　291-293　2009/08

DOI： 10.1016/j.clim.2009.04.011 　

ISSN： 1521-6616
Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity Peer-reviewed

Tomohiro Kubo, Yuki Uchida, Yuko Watanabe, Masahiro Abe, Akira Nakamura, Masao Ono, Shizuo Akira, Toshiyuki Takai

JOURNAL OF EXPERIMENTAL MEDICINE　206　(9)　1971-1982　2009/08

DOI： 10.1084/jem.20082392 　

ISSN： 0022-1007
An activating and inhibitory signal from an inhibitory receptor LMIR3/CLM-1: LMIR3 augments lipopolysaccharide response through association with FcRgamma in mast cells. International-journal Peer-reviewed

Kumi Izawa, Jiro Kitaura, Yoshinori Yamanishi, Takayuki Matsuoka, Ayako Kaitani, Masahiro Sugiuchi, Mariko Takahashi, Akie Maehara, Yutaka Enomoto, Toshihiko Oki, Toshiyuki Takai, Toshio Kitamura

Journal of immunology (Baltimore, Md. : 1950)　183　(2)　925-36　2009/07/15

DOI： 10.4049/jimmunol.0900552 　

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Leukocyte mono-Ig-like receptor 3 (LMIR3) is an inhibitory receptor mainly expressed in myeloid cells. Coengagement of Fc epsilonRI and LMIR3 impaired cytokine production in bone marrow-derived mast cells (BMMCs) induced by Fc epsilonRI crosslinking alone. Mouse LMIR3 possesses five cytoplasmic tyrosine residues (Y241, Y276, Y289, Y303, Y325), among which Y241 and Y289 (Y241/289) or Y325 fit the consensus sequence of ITIM or immunotyrosine-based switch motif (ITSM), respectively. The inhibitory effect was abolished by the replacement of Y325 in addition to Y241/289 with phenylalanine (Y241/189/325/F) in accordance with the potential of Y241/289/325 to cooperatively recruit Src homology region 2 domain-containing phosphatase 1 (SHP)-1 or SHP-2. Intriguingly, LMIR3 crosslinking alone induced cytokine production in BMMCs expressing LMIR3 (Y241/276/289/303/325F) mutant as well as LMIR3 (Y241/289/325F). Moreover, coimmunoprecipitation experiments revealed that LMIR3 associated with ITAM-containing FcRgamma. Analysis of FcRgamma-deficient BMMCs demonstrated that both Y276/303 and FcRgamma played a critical role in the activating function of this inhibitory receptor. Importantly, LMIR3 crosslinking enhanced cytokine production of BMMCs stimulated by LPS, while suppressing production stimulated by other TLR agonists or stem cell factor. Thus, an inhibitory receptor LMIR3 has a unique property to associate with FcRgamma and thereby functions as an activating receptor in concert with TLR4 stimulation.
Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and beta-catenin Peer-reviewed

Karel Otero, Isaiah R. Turnbull, Pietro Luigi Poliani, William Vermi, Elisa Cerutti, Taiki Aoshi, Ilaria Tassi, Toshiyuki Takai, Samuel L. Stanley, Mark Miller, Andrey S. Shaw, Marco Colonna

NATURE IMMUNOLOGY　10　(7)　734-U90　2009/07

DOI： 10.1038/ni.1744 　

ISSN： 1529-2908
Peroxiredoxin III-deficiency Sensitizes Macrophages to Oxidative Stress Peer-reviewed

Lianqin Li, Tomonori Kaifu, Masuo Obinata, Toshiyuki Takai

JOURNAL OF BIOCHEMISTRY　145　(4)　425-427　2009/04

DOI： 10.1093/jb/mvp011 　

ISSN： 0021-924X
DAP10 associates with Ly49 receptors but contributes minimally to their expression and function in vivo Peer-reviewed

Ilaria Tassi, Gaelle Le Friec, Susan Gilfillan, Toshiyuki Takai, Wayne M. Yokoyama, Marco Colonna

EUROPEAN JOURNAL OF IMMUNOLOGY　39　(4)　1129-1135　2009/04

DOI： 10.1002/eji.200838972 　

ISSN： 0014-2980
Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection Peer-reviewed

Mark T. Orr, Joseph C. Sun, David G. T. Hesslein, Hisashi Arase, Joseph H. Phillips, Toshiyuki Takai, Lewis L. Lanier

JOURNAL OF EXPERIMENTAL MEDICINE　206　(4)　807-817　2009/04

DOI： 10.1084/jem.20090168 　

ISSN： 0022-1007
Role of Fc Receptors as a therapeutic target. International-journal Peer-reviewed

Atsuhiro Masuda, Masaru Yoshida, Hideyuki Shiomi, Yoshinori Morita, Hiromu Kutsumi, Hideto Inokuchi, Shigeto Mizuno, Akira Nakamura, Toshiyuki Takai, Richard S Blumberg, Takeshi Azuma

Inflammation & allergy drug targets　8　(1)　80-6　2009/03

DOI： 10.2174/187152809787582525 　

eISSN： 2212-4055

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It has been forty years since the discovery of Fc Receptors and their function. Fc Receptors include the IgG receptors (FcgammaR), high-affinity IgE receptor (FcepsilonRI), IgA and IgA/IgM receptors, and neonatal Fc receptor for IgG (FcRn). In particular, the FcgammaRs have been well known to play an important role in many biologic processes including those associated with the response to infection and cancer as well as in the pathogenesis of immune-mediated diseases. Both positive and negative regulatory function has ascribed to Fc receptors and FcgammaRs in particular which serve to establish a threshold for immune cell activation. In other cases, Fc receptors such as FcRn possess a novel structure and function by playing a major role in the transport of IgG across polarized epithelial barriers at mucosal surfaces and in the regulation of IgG half-life. These diverse functions highlight the potential effectiveness of targeting Fc receptors for therapeutic purposes. This review summarizes new information available in the therapeutic applications of this biology.
Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12 Peer-reviewed

Masanori Inui, Yuki Kikuchi, Naoko Aoki, Shota Endo, Tsutomu Maeda, Akiko Sugahara-Tobinai, Shion Fujimura, Akira Nakamura, Atsushi Kumanogoh, Marco Colonna, Toshiyuki Takai

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　106　(12)　4816-4821　2009/03

DOI： 10.1073/pnas.0900463106 　

ISSN： 0027-8424
Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils Peer-reviewed

Shigeaki Hida, Sho Yamasaki, Yuzuru Sakamoto, Masaya Takamoto, Kazushige Obata, Toshiyuki Takai, Hajime Karasuyama, Kazuo Sugane, Takashi Saito, Shinsuke Taki

NATURE IMMUNOLOGY　10　(2)　214-222　2009/02

DOI： 10.1038/ni.1686 　

ISSN： 1529-2908
骨疾患とシグナル伝達 ITAM型免疫レセプターによる骨ホメオスターシスの制御

高井俊行, 乾匡範, 藤村紫音, 遠藤章太, 中村晃

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　81回・31回　3S6-4　2008/11
Publisher: (公社)日本生化学会
Essential Role of DAP12 Signaling in Macrophage Programming into a Fusion-Competent State Peer-reviewed

Laura Helming, Elena Tomasello, Themis R. Kyriakides, Fernando O. Martinez, Toshiyuki Takai, Siamon Gordon, Eric Vivier

SCIENCE SIGNALING　1　(43)　ra11-ra11　2008/10

DOI： 10.1126/scisignal.1159665 　

ISSN： 1937-9145
Inhibitory immunoglobulin-like receptors LILRB and PIR-B negatively regulate osteoclast development Peer-reviewed

Yu Mori, Sukenao Tsuji, Masanori Inui, Yuzuru Sakamoto, Shota Endo, Yumi Ito, Shion Fujimura, Takako Koga, Akira Nakamura, Hiroshi Takayanagi, Eiji Itoi, Toshiyuki Takai

Journal of Immunology　181　(7)　4742-4751　2008/10/01

DOI： 10.4049/jimmunol.181.7.4742 　

ISSN： 0022-1767

eISSN： 1550-6606
A novel regulatory role of gp49B on dendritic cells in T-cell priming Peer-reviewed

Satoshi Kasai, Masanori Inui, Kyohei Nakamura, Yuta Kakizaki, Shota Endo, Akira Nakamura, Sadayoshi Ito, Toshiyuki Takai

EUROPEAN JOURNAL OF IMMUNOLOGY　38　(9)　2426-2437　2008/09

DOI： 10.1002/eji.200737550 　

ISSN： 0014-2980
PIR-B-deficient mice are susceptible to Salmonella infection Peer-reviewed

Ikuko Torii, Satoshi Oka, Muneki Hotomi, William H. Benjamin, Toshiyuki Takai, John F. Kearney, David F. Briles, Hiromi Kubagawa

JOURNAL OF IMMUNOLOGY　181　(6)　4229-4239　2008/09

DOI： 10.4049/jimmunol.181.6.4229 　

ISSN： 0022-1767
Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells Peer-reviewed

Shota Endo, Yuzuru Sakamoto, Eiji Kobayashi, Akira Nakamura, Toshiyuki Takai

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　105　(38)　14515-14520　2008/09

DOI： 10.1073/pnas.0804571105 　

ISSN： 0027-8424
Comparison of 30 immunity-related genes from the common marmoset with orthologues from human and muse Peer-reviewed

Kazuyoshi Kohu, Eiji Yamabe, Ayako Matsuzawa, Daisuke Onda, Hiroshi Suemizu, Erika Sasaki, Yoshikuni Tanioka, Hideo Yagita, Daisuke Suzuki, Yoshie Kametani, Toshiyuki Takai, Atsushi Toyoda, Sonoko Habu, Masanobu Satake

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　215　(2)　167-180　2008/06

DOI： 10.1620/tjem.215.167 　

ISSN： 0040-8727

eISSN： 1349-3329
イムノロジーからリウマトロジーへのメッセージ Fc受容体と自己免疫

高井俊行, 井上吉浩, 海部知則, 遠藤章太, 中村晃

日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集　52回・17回　192-192　2008/04
Publisher: (一社)日本リウマチ学会
Fc gamma receptor regulation of Citrobacter rodentium infection Peer-reviewed

Atsuhiro Masuda, Masaru Yoshida, Hideyuki Shiomi, Satoshi Ikezawa, Tetsuya Takagawa, Hiroshi Tanaka, Ryo Chinzei, Tsukasa Ishida, Yoshinori Morita, Hiromu Kutsumi, Hideto Inokuchi, Shuo Wang, Kanna Kobayashi, Shigeto Mizuno, Akira Nakamura, Toshiyuki Takai, Richard S. Blumberg, Takeshi Azuma

INFECTION AND IMMUNITY　76　(4)　1728-1737　2008/04

DOI： 10.1128/IAI.01493-07 　

ISSN： 0019-9567
Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Peer-reviewed

Masahiro Shinohara, Takako Koga, Kazuo Okamoto, Shinya Sakaguchi, Kimiko Arai, Hisataka Yasuda, Toshiyuki Takai, Tatsuhiko Kodama, Tomohiro Morio, Raif S Geha, Daisuke Kitamura, Tomohiro Kurosaki, Wilfried Ellmeier, Hiroshi Takayanagi

Cell　132　(5)　794-806　2008/03

DOI： 10.1016/j.cell.2007.12.037 　

ISSN： 1097-4172
Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals Peer-reviewed

Masahiro Shinohara, Takako Koga, Kazuo Okamoto, Shinya Sakaguchi, Kimiko Arai, Hisataka Yasuda, Toshiyuki Takai, Tatsuhiko Kodama, Tomohiro Morio, Raif S. Geha, Daisuke Kitamura, Tomohiro Kurosaki, Wilfried Ellmeier, Hiroshi Takayanagi

CELL　132　(5)　794-806　2008/03

DOI： 10.1016/j.cell.2007.12.037 　

ISSN： 0092-8674
Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells. International-journal Peer-reviewed

Yoshinori Yamanishi, Jiro Kitaura, Kumi Izawa, Takayuki Matsuoka, Toshihiko Oki, Yang Lu, Fumi Shibata, Satoshi Yamazaki, Hidetoshi Kumagai, Hideaki Nakajima, Mari Maeda-Yamamoto, Victor L J Tybulewicz, Toshiyuki Takai, Toshio Kitamura

Blood　111　(2)　688-98　2008/01/15

DOI： 10.1182/blood-2007-04-085787 　

ISSN： 0006-4971
【骨と免疫】免疫グロブリン様受容体と骨代謝

高井俊行, 乾匡範, 森優

腎と骨代謝　21　(1)　43-50　2008/01
Publisher: (株)日本メディカルセンター
ISSN： 0914-5265

eISSN： 2433-2496
Fc Receptor Targeting in the Treatment of Allergy, Autoimmune Diseases and Cancer Peer-reviewed

Akira Nakamura, Tomohiro Kubo, Toshiyuki Takai

MULTICHAIN IMMUNE RECOGNITION RECEPTOR SIGNALING: FROM SPATIOTEMPORAL ORGANIZATION TO HUMAN DISEASE　640　220-233　2008

DOI： 10.1007/978-0-387-09789-3_17 　

ISSN： 0065-2598
Regulation of immune disorders by PIR-B, a critical inhibitory Ig-like receptor for MHC class I molecules Peer-reviewed

Toshiyuki Takai, Akira Nakamura, Shota Endo, Tomohiro Kubo

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN　128　41-42　2008

ISSN： 0031-6903
Phosphatidylinositol 3-kinase activation is required to form the NKG2D immunological synapse Peer-reviewed

Emanuele Giurisato, Marina Cella, Toshiyuki Takai, Tomohiro Kurosaki, Yungfeng Feng, Gregory D. Longmore, Marco Colonna, Andrey S. Shaw

MOLECULAR AND CELLULAR BIOLOGY　27　(24)　8583-8599　2007/12

DOI： 10.1128/MCB.01477-07 　

ISSN： 0270-7306
Mast cells and basophils are selectively activated in vitro and in vivo through CD200R3 in an IgE-Independent manner Peer-reviewed

Toshiyuki Kojima, Kazushige Obata, Kaori Mukai, Shingo Sato, Toshiyuki Takai, Yoshiyuki Minegishi, Hajime Karasuyama

JOURNAL OF IMMUNOLOGY　179　(10)　7093-7100　2007/11

DOI： 10.4049/jimmunol.179.10.7093 　

ISSN： 0022-1767
PIR-B-deficient mice are susceptible to salmonella infection Peer-reviewed

Satoshi Oka, Ikuko Torii, Muneki Hotomi, William H. Benjamin, Toshiyuki Takai, John F. Kearney, David E. Briles, Hiromi Kubagawa

BLOOD　110　(11)　714A-714A　2007/11

ISSN： 0006-4971
Critical negative regulation of immunopathology by signaling intracellular infection Peer-reviewed

Maziar Divangahi, Tony Yang, Kapilan Kugathasan, Sarah McCormick, Shunsuke Takenaka, Gordon Gaschler, Ali Ashkar, Martin Stampfli, Jack Gauldie, Jonathan Bramson, Toshiyuki Takai, Earl Brown, Wayne M. Yokoyama, Naoko Aoki, Zhou Xing

JOURNAL OF IMMUNOLOGY　179　(6)　4015-4026　2007/09

DOI： 10.4049/jimmunol.179.6.4015 　

ISSN： 0022-1767
Pathological role of osteoclast costimulation in arthritis-induced bone loss Peer-reviewed

Sae Ochi, Masahiro Shinohara, Kojiro Sato, Hans-Juergen Gober, Takako Koga, Tatsuhiko Kodama, Toshiyuki Takai, Nobuyuki Miyasaka, Hiroshi Takayanagi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　104　(27)　11394-11399　2007/07

DOI： 10.1073/pnas.0701971104 　

ISSN： 0027-8424
Activating Fc gamma receptors participate in the development of autoimmune diabetes in NOD mice Peer-reviewed

Yoshihiro Inoue, Tomonori Kaifu, Akiko Sugahara-Tobinai, Akira Nakamura, Jun-Ichi Miyazaki, Toshiyuki Takai

JOURNAL OF IMMUNOLOGY　179　(2)　764-774　2007/07

DOI： 10.4049/jimmunol.179.2.764 　

ISSN： 0022-1767
Functional analysis of activating receptor LMIR4 as a counterpart of inhibitory receptor LMIR3. International-journal Peer-reviewed

Kumi Izawa, Jiro Kitaura, Yoshinori Yamanishi, Takayuki Matsuoka, Toshihiko Oki, Fumi Shibata, Hidetoshi Kumagai, Hideaki Nakajima, Mari Maeda-Yamamoto, Jeffrey P Hauchins, Victor L J Tybulewicz, Toshiyuki Takai, Toshio Kitamura

The Journal of biological chemistry　282　(25)　17997-8008　2007/06/22

DOI： 10.1074/jbc.M701100200 　

ISSN： 0021-9258
The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors Peer-reviewed

Hiromitsu Hara, Chitose Ishihara, Arata Takeuchi, Takayuki Imanishi, Liquan Xue, Stephan W. Morris, Masanori Inui, Toshiyuki Takai, Akira Shibuya, Shinobu Saijo, Yoichiro Iwakura, Naohito Ohno, Haruhiko Koseki, Hiroki Yoshida, Josef M. Penninger, Takashi Saito

NATURE IMMUNOLOGY　8　(6)　619-629　2007/06

DOI： 10.1038/ni1466 　

ISSN： 1529-2908
Paired Ig-like receptors bind to bacteria and shape TLR-mediated cytokine production Peer-reviewed

Masafumi Nakayama, David M. Underhill, Timothy W. Petersen, Bin Li, Toshio Kitamura, Toshiyuki Takai, Alan Aderem

JOURNAL OF IMMUNOLOGY　178　(7)　4250-4259　2007/04

DOI： 10.4049/jimmunol.178.7.4250 　

ISSN： 0022-1767
Increased susceptibility of MER5 (peroxiredoxin III) knockout mice to LPS-induced oxidative stress Peer-reviewed

Lianqin Li, Wataru Shoji, Hirohisa Takano, Noriko Nishimura, Yasunobu Aoki, Ryoya Takahashi, Sataro Goto, Tomonori Kaifu, Toshiyuki Takai, Masuo Obinata

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　355　(3)　715-721　2007/04

DOI： 10.1016/j.bbrc.2007.02.022 　

ISSN： 0006-291X
Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation Peer-reviewed

Ai Masuda, Akira Nakamura, Tsutomu Maeda, Yuzuru Sakamoto, Toshiyuki Takai

JOURNAL OF EXPERIMENTAL MEDICINE　204　(4)　907-920　2007/04

DOI： 10.1084/jem.20060631 　

ISSN： 0022-1007
Susceptibility of PIR-B deficient mice to Salmonella infection Peer-reviewed

Ikuko Torii, Satoshi Oka, Muneki Hotomi, William H. Benjamin, John F. Kearney, Toshiyuki Takai, David E. Briles, Hiromi Kubagawa

JOURNAL OF IMMUNOLOGY　178　2007/04

ISSN： 0022-1767

eISSN： 1550-6606
Dual assemblies of an activating immune receptor, MAIR-II, with ITAM-bearing adapters DAP12 and FcR gamma chain on peritoneal macrophages Peer-reviewed

Chigusa Nakahashi, Satoko Tahara-Hanaoka, Naoya Totsuka, Yasushi Okoshi, Toshiyuki Takai, Nobuhiro Ohkohchi, Shin-ichiro Honda, Kazuko Shibuya, Akira Shibuya

JOURNAL OF IMMUNOLOGY　178　(2)　765-770　2007/01

DOI： 10.4049/jimmunol.178.2.765 　

ISSN： 0022-1767
Critical role of the Fc receptor gamma-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation Peer-reviewed

Kenichi Kitamura, Katsuyuki Takeda, Toshiyuki Koya, Nobuaki Miyahara, Taku Kodama, Azzeddine Dakhama, Toshiyuki Takai, Atsushi Hirano, Mitsune Tanimoto, Mine Harada, Erwin W. Gelfand

JOURNAL OF IMMUNOLOGY　178　(1)　480-488　2007/01

DOI： 10.4049/jimmunol.178.1.480 　

ISSN： 0022-1767
【シグナル伝達病を知るその分子機序解明から新たな治療戦略まで】基礎編免疫系のシグナル伝達 FcRを介するシグナル伝達

中村晃, 高井俊行

遺伝子医学MOOK　(6)　51-54　2006/12
Publisher: (株)メディカルドゥ
ISSN： 1349-2527
Fc receptors: their diverse functions in immunity and immune disorders Peer-reviewed

Toshiyuki Takai

SPRINGER SEMINARS IN IMMUNOPATHOLOGY　28　(4)　303-304　2006/12

DOI： 10.1007/s00281-006-0055-y 　

ISSN： 0344-4325
Regulation of osteoclast differentiation and function by the CaMK-CREB pathway Peer-reviewed

Kojiro Sato, Ayako Suematsu, Tomoki Nakashima, Sayaka Takemoto-Kimura, Kazuhiro Aoki, Yasuyuki Morishita, Hiroshi Asahara, Keiichi Ohya, Akira Yamaguchi, Toshiyuki Takai, Tatsuhiko Kodama, Talal A. Chatila, Haruhiko Bito, Hiroshi Takayanagi

NATURE MEDICINE　12　(12)　1410-1416　2006/12

DOI： 10.1038/nm1515 　

ISSN： 1078-8956
関節リウマチ〜基礎解析からの新知見炎症性骨破壊における免疫受容体と新たな治療戦略の可能性について

越智小枝, 篠原正浩, 佐藤浩二郎, 高井俊行, 宮坂信之, 高柳広

日本免疫学会総会・学術集会記録　36　284-284　2006/11
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
Establishment and functional characterization of novel natural killer cell lines derived from a temperature-sensitive SV40 large T antigen transgenic mouse Peer-reviewed

Satoru Iizuka, Tomonori Kaifu, Akira Nakamura, Masuo Obinata, Toshiyuki Takai

JOURNAL OF BIOCHEMISTRY　140　(2)　255-265　2006/08

DOI： 10.1093/jb/mvj153 　

ISSN： 0021-924X
Novel mast cell lines with enhanced proliferative and degranulative abilities established from temperature-sensitive SV40 large T antigen transgenic mice Peer-reviewed

Masahiko Kanehira, Tomonori Kaifu, Kozue Maya, Mitsuji Kaji, Akira Nakamura, Masuo Obinata, Toshiyuki Takai

JOURNAL OF BIOCHEMISTRY　140　(2)　211-220　2006/08

DOI： 10.1093/jb/mvj140 　

ISSN： 0021-924X
【炎症と破骨細胞】破骨細胞を制御するレセプター群 Invited

森優, 乾匡範, 高井俊行

炎症と免疫　14　(5)　615-619　2006/08
Publisher:
ISSN： 0918-8371
Vav1 controls DAP10-mediated natural cytotoxicity by regulating actin and microtubule dynamics Peer-reviewed

Daniel B. Graham, Marina Cella, Emanuele Giurisato, Keiko Fujikawa, Ana V. Miletic, Tracie Kloeppel, Karry Brim, Toshiyuki Takai, Andrey S. Shaw, Marco Colonna, Wojciech Swat

JOURNAL OF IMMUNOLOGY　177　(4)　2349-2355　2006/08

DOI： 10.4049/jimmunol.177.4.2349 　

ISSN： 0022-1767
Fcγレセプターを介した免疫制御 Invited

窪智宏, 中村晃, 高井俊行

臨床免疫・アレルギー科　46　(1)　106-111　2006/07
Publisher:
ISSN： 1881-1930
Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis Peer-reviewed

N Takegahara, H Takamatsu, T Toyofuku, T Tsujimura, T Okuno, K Yukawa, M Mizui, M Yamamoto, DVR Prasad, K Suzuki, M Ishii, K Terai, M Moriya, Y Nakatsuji, S Sakoda, S Sato, S Akira, K Takeda, M Inui, T Takai, M Ikawa, M Okabe, A Kumanogoh, H Kikutani

NATURE CELL BIOLOGY　8　(6)　615-622　2006/06

DOI： 10.1038/ncb1416 　

ISSN： 1465-7392

eISSN： 1476-4679
【分子メカニズムから解き明かす疾患のサイエンス】免疫(アレルギー)疾患免疫応答とアレルギー抑制型受容体によるアレルギー制御 Invited

中村晃, 高井俊行

実験医学　24　(10)　1535-1539　2006/06
Publisher:
ISSN： 0288-5514
A critical role of Fc gamma receptors in the development of autoimmune type 1 diabetes of NOD mice Peer-reviewed

Yoshihiro Inoue, Akira Nakamura, Toshiyuki Takai

JOURNAL OF IMMUNOLOGY　176　S132-S132　2006/04

ISSN： 0022-1767
Constitutive binding of PIR-B to MHC class I in cis regulates mast cell activation and anaphylaxis Peer-reviewed

Akira Nakamura, Toshiyuki Takai

JOURNAL OF IMMUNOLOGY　176　S321-S321　2006/04

ISSN： 0022-1767
【加齢の生化学】破骨細胞の分化制御機構と骨疾患 Invited

乾匡範, 森優, 高井俊行

生化学　78　(3)　250-256　2006/03
Publisher:
ISSN： 0037-1017
Siglec-H is an IPC-specific receptor that modulates type IIFN secretion through DAP12 Peer-reviewed

AL Blasius, M Cella, J Maldonado, T Takai, M Colonna

BLOOD　107　(6)　2474-2476　2006/03

DOI： 10.1182/blood-2005-09-3746 　

ISSN： 0006-4971
目でみるバイオサイエンスガンマグロブリン大量療法の作用機序 Invited

窪智宏, 中村晃, 高井俊行

内科　97　(1)　155-158　2006/01
Publisher:
ISSN： 0022-1961
A role for high molecular weight mast cell-derived proteoglycans in mucosal immunity against gastrointestinal nematode parasites. Peer-reviewed

Denchris Onah, Fukumi Nakamura-Uchiyama, Masao Ono, Toshiyuki Takai, Yukifumi Nawa

CLINICAL IMMUNOLOGY　119　S175-S175　2006

DOI： 10.1016/j.clim.2006.04.472 　

ISSN： 1521-6616
加齢による免疫機構の変化と抑制性レセプター Invited

中村晃, 高井俊行

生体の科学　56　(6)　639-645　2005/12

DOI： 10.11477/mf.2425100424 　
Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b(-/-)Pdcd1(-/-) mice Peer-reviewed

T Okazaki, Y Otaka, J Wang, H Hiai, T Takai, JV Ravetch, T Honjo

JOURNAL OF EXPERIMENTAL MEDICINE　202　(12)　1643-1648　2005/12

DOI： 10.1084/jem.20051984 　

ISSN： 0022-1007
イムノグロブリン様レセプターによる免疫制御 Invited

高井俊行

Medical Science Digest　31　(12)　458-459　2005/11
Allergy and autoimmunity mediated by IgG and Fcγ receptors Peer-reviewed

Toshiyuki Takai

Japanese Journal of Allergology　54　(10)　1183-1189　2005/10

ISSN： 0021-4884 1347-7935
Pathways participating in activation of mouse uterine natural killer cells during pregnancy Peer-reviewed

XM Xie, H He, M Colonna, T Seya, T Takai, BA Croy

BIOLOGY OF REPRODUCTION　73　(3)　510-518　2005/09

DOI： 10.1095/biolreprod.104.033951 　

ISSN： 0006-3363
【関節リウマチの最新動向骨免疫学的視点からの病因論・治療学】破骨細胞分化機構 IgLRによる破骨細胞の分化制御 Invited

高井俊行, 乾匡範, 井上和也, 森優

日本臨床　63　(9)　1562-1568　2005/09
Publisher:
ISSN： 0047-1852
DAP12 (KARAP) amplifies inflammation and increases mortality from endotoxemia and septic peritonitis Peer-reviewed

IR Turnbull, JE McDunn, T Takai, RR Townsend, JP Cobb, M Colonna

JOURNAL OF EXPERIMENTAL MEDICINE　202　(3)　363-369　2005/08

DOI： 10.1084/jem.20050986 　

ISSN： 0022-1007
イムノグロブリン様受容体による免疫制御と免疫疾患に関する研究 Invited

高井俊行

東北医学雑誌　117　(1)　115-116　2005/06
【免疫と疾患(後篇) 自己免疫と疾患】自己免疫疾患の基礎 Fc受容体の異常 Invited

高井俊行

最新医学　60　(6月増刊)　1322-1332　2005/06
【自己免疫疾患研究の最先端】病態免疫グロブリン受容体と自己免疫疾患 Invited

高井俊行

医学のあゆみ　213　(1)　52-58　2005/04
The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B Peer-reviewed

H Zhang, FY Meng, CL Chu, T Takai, CA Lowell

IMMUNITY　22　(2)　235-246　2005/02

DOI： 10.1016/j.immuni.2005.01.004 　

ISSN： 1074-7613
GVH病におけるpaired immunoglobulin-like receptor B(PIR-B)の役割 Invited

小林栄治, 中村晃, 高井俊行

臨床免疫　43　(2)　215-218　2005/02
Publisher:
ISSN： 0386-9695
呼吸器系の生物学マスト細胞とFcレセプター Invited

遠藤章太, 中村晃, 高井俊行

Annual Review呼吸器　2005　26-32　2005/01
Role of Fcγ receptors in immune regulation and diseases Invited

Toshiyuki Takai

Japanese Journal of Clinical Immunology　28　(5)　318-326　2005

DOI： 10.2177/jsci.28.318 　

ISSN： 1349-7413 0911-4300
【免疫2005】病気と免疫自己免疫の治療ターゲットとしてのFcγR II B Invited

高井俊行, 中村晃

Molecular Medicine　41　(臨増)　385-392　2004/12
【関節炎の動物モデル】 Fcレセプターと関節炎 Invited

後藤義幸, 中村晃, 高井俊行

分子リウマチ　1　(4)　302-308　2004/11
The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage integrin signaling Peer-reviewed

S Pereira, H Zhang, T Takai, CA Lowell

JOURNAL OF IMMUNOLOGY　173　(9)　5757-5765　2004/11

ISSN： 0022-1767
Immortalized dendritic cell line with efficient cross-priming ability established from transgenic mice harboring the temperature-sensitive SV40 large T-Antigen gene Peer-reviewed

S Ebihara, S Endo, K Ito, Y Ito, Y Ito, K Akiyama, M Obinata, T Takai

JOURNAL OF BIOCHEMISTRY　136　(3)　321-328　2004/09

DOI： 10.1093/jb/mvh120 　

ISSN： 0021-924X
ピアによるGVHDの制御 Invited

高井俊行

医学のあゆみ　210　(9)　776-777　2004/08
Exacerbated graft-versus-host disease in Pirb(-/-) mice Peer-reviewed

A Nakamura, E Kobayashi, T Takai

NATURE IMMUNOLOGY　5　(6)　623-629　2004/06

DOI： 10.1038/ni1074 　

ISSN： 1529-2908
抑制性免疫グロブリン受容体FcγRIIBと自己免疫疾患 Invited

高井俊行, 矢島佳央里, 後藤義幸, 中村晃

小児感染免疫　16　(1)　69-77　2004/04

ISSN： 0917-4931
Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis Peer-reviewed

T Koga, M Inui, K Inoue, S Kim, A Suematsu, E Kobayashi, T Iwata, H Ohnishi, T Matozaki, T Kodama, T Taniguchi, H Takayanagi, T Takai

NATURE　428　(6984)　758-763　2004/04

DOI： 10.1038/nature02444 　

ISSN： 0028-0836
SLPIノックアウトマウス Invited

中村晃, 高井俊行, 貫和敏博

分子呼吸器病　8　(2)　140-144　2004/03
Publisher:
ISSN： 1342-436X
【骨免疫学の世界骨疾患と免疫異常】免疫グロブリン様受容体と骨疾患 Invited

乾匡範, 井上和也, 高井俊行

医学のあゆみ　208　(11)　910-915　2004/03
Publisher:
ISSN： 0039-2359
Roles of FcγRIIB in Nasal Eosinophilia and IgE Production in Murine Allergic Rhinitis Peer-reviewed

Tohru Watanabe, Mitsuhiro Okano, Hisashi Hattori, Tadashi Yoshino, Nobuaki Ohno, Nobuo Ohta, Yuji Sugata, Yorihisa Orita, Toshiyuki Takai, Kazunori Nishizaki

American Journal of Respiratory and Critical Care Medicine　169　(1)　105-112　2004/01/01

DOI： 10.1164/rccm.200302-239oc 　

ISSN： 0003-0805
Immunoglobulin-like receptors in myeloid cells: The functional regulation and the involvement in disorders Invited Peer-reviewed

Sakamoto Y, Kaifu T, Uehori J, Nakamura A, Takai T

Recent Research Developments in Immunology　(6)　355-371　2004
Possible role of autoantibodies in the pathophysiology of GM2 gangliosidoses Peer-reviewed

A Yamaguchi, K Katsuyama, K Nagahama, T Takai, Aoki, I, S Yamanaka

JOURNAL OF CLINICAL INVESTIGATION　113　(2)　200-208　2004/01

DOI： 10.1172/JCI200419639 　

ISSN： 0021-9738
【アレルギーに関する新知見】 I型アレルギーにおけるPIR-Bの役割 Invited

増田愛, 前田努, 中村晃, 高井俊行

臨床免疫　41　(1)　43-48　2004/01
Roles of Fc gamma RIIB in nasal eosinophilia and IgE production in murine allergic rhinitis Peer-reviewed

T Watanabe, M Okano, H Hattori, T Yoshino, N Ohno, N Ohta, Y Sugata, Y Orita, T Takai, K Nishizaki

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　169　(1)　105-112　2004/01

DOI： 10.1164/rccm.200302-2390C 　

ISSN： 1073-449X
【免疫2004】抗原認識 PIR-Bと樹状細胞の成熟 Invited

中村晃, 高井俊行

Molecular Medicine　40　(臨増)　65-72　2003/12
Publisher:
ISSN： 0918-6557
炎症反応の制御とプロテアーゼ阻害因子 Invited

中村晃, 高井俊行, 貫和敏博

臨床免疫　40　(5)　576-579　2003/11
Publisher:
ISSN： 0386-9695
【アレルギーの動物モデル】 PIR-B欠損マウス Invited

増田愛, 前田努, 中村晃, 高井俊行

アレルギー科　16　(4)　295-300　2003/10
Accelerated antigen presentation and elicitation of humoral response in vivo by Fc gamma RIIB- and Fc gamma RI/III-mediated immune complex uptake Peer-reviewed

A Yada, S Ebihara, K Matsumura, S Endo, T Maeda, A Nakamura, K Akiyama, S Aiba, T Takai

CELLULAR IMMUNOLOGY　225　(1)　21-32　2003/09

DOI： 10.1016/j.cellimm.2003.09.008 　

ISSN： 0008-8749
【NK・NKT細胞をめぐって】活性化アダプター分子DAP12の機能 Invited

乾匡範, 高井俊行

臨床免疫　40　(3)　309-313　2003/09
Publisher:
ISSN： 0386-9695
Signaling via immunoglobulin Fc receptors induces oligodendrocyte precursor cell differentiation Peer-reviewed

J Nakahara, K Tan-Takeuchi, C Seiwa, M Gotoh, T Kaifu, A Ujike, M Inui, T Yagi, M Ogawa, S Aiso, T Takai, H Asou

DEVELOPMENTAL CELL　4　(6)　841-852　2003/06

DOI： 10.1016/S1534-5807(03)00155-2 　

ISSN： 1534-5807
Deregulation of peripheral B-cell development in enhanced severity of collagen-induced arthritis in Fc gamma RIIB-deficient mice Peer-reviewed

A Nakamura, T Nukiwa, T Takai

JOURNAL OF AUTOIMMUNITY　20　(3)　227-236　2003/05

DOI： 10.1016/S0896-8411(03)00034-9 　

ISSN： 0896-8411
【B細胞レセプターシグナルを修飾する表面分子】 PIR-BによるB細胞の制御機構 Invited

中村晃, 高井俊行

臨床免疫　39　(5)　519-524　2003/05
Fc gamma RIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease Peer-reviewed

K Yajima, A Nakamura, A Sugahara, T Takai

EUROPEAN JOURNAL OF IMMUNOLOGY　33　(4)　1020-1029　2003/04

DOI： 10.1002/eji.200323794 　

ISSN： 0014-2980
Transient neutrophil infiltration after allergen challenge is dependent on specific antibodies and Fc gamma III receptors Peer-reviewed

C Taube, A Dakhama, YH Rha, K Takeda, A Joetham, JW Park, A Balhorn, T Takai, KR Poch, JA Nick, EW Gelfand

JOURNAL OF IMMUNOLOGY　170　(8)　4301-4309　2003/04

ISSN： 0022-1767
Targeting of platelet integrin alpha(IIb)beta(3) determines systemic reaction and bleeding in murine thrombocytopenia regulated by activating and inhibitory Fc gamma R Peer-reviewed

B Nieswandt, W Bergmeier, Schulte, V, T Takai, U Baumann, RE Schmidt, H Zirngibl, W Bloch, JE Gessner

INTERNATIONAL IMMUNOLOGY　15　(3)　341-349　2003/03

DOI： 10.1093/intimm/dxg033 　

ISSN： 0953-8178
アレルギー反応におけるPaired Immunoglobulin-like Receptor(PIR)-Bの役割 Invited

増田愛, 中村晃, 高井俊行

アレルギー科　15　(3)　228-232　2003/03
Increased susceptibility to LPS-induced endotoxin shock in secretory leukoprotease inhibitor (SLPI)-deficient mice Peer-reviewed

A Nakamura, Y Mori, K Hagiwara, T Suzuki, T Sakakibara, T Kikuchi, T Igarashi, M Ebina, J Miyazaki, T Takai, T Nukiwa, T Nukiwa

JOURNAL OF EXPERIMENTAL MEDICINE　197　(5)　669-674　2003/03

DOI： 10.1084/jem.20021824 　

ISSN： 0022-1007
Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice Peer-reviewed

T Kaifu, J Nakahara, M Inui, K Mishima, T Momiyama, M Kaji, A Sugahara, H Koito, A Ujike-Asai, A Nakamura, K Kanazawa, K Tan-Takeuchi, K Iwasaki, WM Yokoyama, A Kudo, M Fujiwara, H Asou, T Takai

JOURNAL OF CLINICAL INVESTIGATION　111　(3)　323-332　2003/02

DOI： 10.1172/JCI200316923 　

ISSN： 0021-9738
【神経疾患と分子病態モデルをめぐるトピックス】髄鞘障害 DAP12欠損とオリゴデンドロサイト発達障害 Invited

高井俊行

Clinical Neuroscience　21　(2)　162-164　2003/02
Targeting apoptotic tumor cells to Fc gamma R provides efficient and versatile vaccination against tumors by dendritic cells Peer-reviewed

K Akiyama, S Ebihara, A Yada, K Matsumura, S Aiba, T Nukiwa, T Takai

JOURNAL OF IMMUNOLOGY　170　(4)　1641-1648　2003/02

DOI： 10.4049/jimmunol.170.4.1641 　

ISSN： 0022-1767
接着,共刺激分子,トラフィッキング,ホーミング Ig-like receptor分子群による免疫細胞の制御

高井俊行, 中村晃

Annual Review免疫　2003　142-150　2002/12
Transcriptional regulation of Fcgr2b gene by polymorphic promoter region and its contribution to humoral immune responses Peer-reviewed

Y Xiu, K Nakamura, M Abe, N Li, XS Wen, Y Jiang, DQ Zhang, H Tsurui, S Matsuoka, Y Hamano, H Fujii, M Ono, T Takai, T Shimokawa, C Ra, T Shirai, S Hirose

JOURNAL OF IMMUNOLOGY　169　(8)　4340-4346　2002/10

ISSN： 0022-1767
The control effect of histamine on body temperature and respiratory function in IgE-dependent systemic anaphylaxis Peer-reviewed

Y Makabe-Kobayashi, Y Hori, T Adachi, S Ishigaki-Suzuki, Y Kikuchi, Y Kagaya, K Shirato, A Nagy, A Ujike, T Takai, T Watanabe, H Ohtsu

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY　110　(2)　298-303　2002/08

DOI： 10.1067/mai.2002.125977 　

ISSN： 0091-6749
Roles of Fc receptors in autoimmunity Peer-reviewed

T Takai

NATURE REVIEWS IMMUNOLOGY　2　(8)　580-592　2002/08

DOI： 10.1038/nri856 　

ISSN： 1474-1733
Impaired dendritic cell maturation and increased T(H)2 responses in PIR-B-/- mice Peer-reviewed

A Ujike, K Takeda, A Nakamura, S Ebihara, K Akiyama, T Takai

NATURE IMMUNOLOGY　3　(6)　542-548　2002/06

DOI： 10.1038/ni801 　

ISSN： 1529-2908
207 FcγRIIBを介する鼻アレルギー感作の制御

渡辺徹, 岡野光博, 服部央, 吉野正, 高井俊行, 西崎和則

アレルギー　51　(9)　958-958　2002
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.51.958_3 　
The pre-B cell receptor signaling for apoptosis is negatively regulated by Fc gamma RIIB Peer-reviewed

Kato, I, T Takai, A Kudo

JOURNAL OF IMMUNOLOGY　168　(2)　629-634　2002/01

ISSN： 0022-1767
The pre-B cell receptor signaling for apoptosis is negatively regulated by Fc gamma RIIB Peer-reviewed

Kato, I, T Takai, A Kudo

JOURNAL OF IMMUNOLOGY　168　(2)　629-634　2002/01

ISSN： 0022-1767
Role of Fc receptor in The Development of Collagen-Induced Arthritis Peer-reviewed

Akira Nakamura, Kaori Yajima, Toshiyuki Takai

Japanese Journal of Clinical Immunology　25　(1)　56-61　2002

DOI： 10.2177/jsci.25.56 　

ISSN： 1349-7413 0911-4300
FcγRIIB欠損(FcgRIIB-/-)及びFcεRIγ-chain(FcRγ-/-)欠損マウス由来マクロファージにおけるプロスタグランジン合成酵素の発現

湯浅貴恵, 横山知永子, 後藤淳子, 内藤久仁子, 高井俊行, 田辺忠

生化学　73　(11)　1351-1351　2001/11
Publisher: (公社)日本生化学会
ISSN： 0037-1017

eISSN： 2189-0544
Drastic up-regulation of Fcepsilonri on mast cells is induced by IgE binding through stabilization and accumulation of Fcepsilonri on the cell surface. Peer-reviewed

S Kubo, K Matsuoka, C Taya, F Kitamura, T Takai, H Yonekawa, H Karasuyama

The Journal of Immunology　167　(6)　3427-3434　2001/10
Lyn is essential for Fcγ receptor III-mediated systemic anaphylaxis but not for the arthus reaction Peer-reviewed

Takae Yuasa, Masao Ono, Takeshi Watanabe, Toshiyuki Takai

Journal of Experimental Medicine　193　(5)　563-571　2001/03/05

DOI： 10.1084/jem.193.5.563 　

ISSN： 0022-1007
FcRとアレルギー(免疫応答の制御機構)

高井俊行

アレルギー　50　(9)　885-885　2001
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.50.885_2 　
318 マウス喘息モデルにおけるFcγRIIIの役割に関する検討

平野淳, 金廣有彦, 北村賢一, 谷本安, 安原信明, 片岡幹男, 谷本光音, 岡田千春, 高橋清, 高井俊行, 武田勝行, Gelfand EW

アレルギー　50　(9)　978-978　2001
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.50.978_2 　
P57W5-3 Defective protection of FcRγ-knockout mice against Strongyloides venezuelensis infection at the intestinal phase is due to the failure of mucosal mast cells to release sulphated proteoglycans

ONAH N Denis, NAKAMURA Fukumi, ISHIWATA Kenji, ONO Masao, TAKAI Toshiyuki, NAWA Yukifumi

Medical Entomology and Zoology　52　92-92　2001
Publisher: The Japan Society of Medical Entomology and Zoology
DOI： 10.7601/mez.52.92_1 　
コラーゲン誘導関節炎におけるFcγレセプターの役割について

中村晃, 湯浅貴恵, 氏家あづさ, 小野栄夫, 貫和敏博, 高井俊行

日本免疫学会総会・学術集会記録　30　171-171　2000/11
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
Stimulatory function of gp49A, a murine Ig-like receptor, in rat basophilic leukemia cells Peer-reviewed

Kwang Ho Lee, M. Ono, M. Inui, T. Yuasa, T. Takai

Journal of Immunology　165　(9)　4970-4977　2000/11/01

ISSN： 0022-1767
関節炎モデルの作製 FcγRIIB欠損DBA/1Jマウスにおける関節炎誘導について

中村晃, 湯浅貴恵, 氏家あづさ, 小野栄夫, 貫和敏博, 高井俊行

炎症　20　(4)　497-497　2000/07
Publisher: (一社)日本炎症・再生医学会
ISSN： 0389-4290

eISSN： 1884-4006
Signal Transduction and Role in Immune Responses for Inhibitory Fc Receptor

ONO Masao, TAKAI Toshiyuki

KAGAKU TO SEIBUTSU　38　(3)　154-160　2000/03/25
Publisher: Japan Society for Bioscience, Biotechnology, and Agrochemistry
DOI： 10.1271/kagakutoseibutsu1962.38.154 　

ISSN： 0453-073X
Fcgamma receptor IIB-deficient mice develop Goodpasture's syndrome upon immunization with type IV collagen: a novel murine model for autoimmune glomerular basement membrane disease. Peer-reviewed

Nakamura A, Yuasa T, Ujike A, Ono M, Nukiwa T, Ravetch JV, Takai T

The Journal of experimental medicine　191　(5)　899-906　2000/03

DOI： 10.1084/jem.191.5.899 　

ISSN： 0022-1007
アレルギー性疾患の発症機序とFcレセプター

高井俊行

アレルギー　49　(9)　794-794　2000
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.49.794_2 　
441 マウス喘息モデルにおける気道炎症に対するFcレセプターの役割

北村賢一, 金廣有彦, 平野淳, 武田明子, 木村五郎, 谷本安, 片岡幹男, 原田実根, 高井俊行, 武田勝行, Erwin W.Gelfand

アレルギー　49　(9)　1003-1003　2000
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.49.1003_1 　
Igファミリーレセプターによる細胞活性化とDAP12

高井俊行, 小野栄夫, 乾匡範, 石川陽子

臨床免疫　33　(1)　130-136　2000/01
Publisher: (有)科学評論社
ISSN： 0386-9695
Interaction between galectin-3 and FcγRII induces down-regulation of IL-5 gene: Implication of the promoter sequence IL-SREIII Peer-reviewed

Isabel Cortegano, Victoria Del Pozo, Blanca Cárdaba, Ignacio Arrieta, Soledad Gallardo, Marta Rojo, Esther Aceituno, Toshiyuki Takai, Sjef Verbeek, Pilar Palomino, Fu-Tong Liu, Carlos Lahoz

Glycobiology　10　(3)　237-242　2000
Publisher: Oxford University Press
DOI： 10.1093/glycob/10.3.237 　

ISSN： 0959-6658
Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcRγ-deficient mice Peer-reviewed

Hisashi Wakayama, Yoshinori Hasegawa, Tsutomu Kawabe, Toru Hara, Seiichi Matsuo, Masashi Mizuno, Toshiyuki Takai, Hitoshi Kikutani, Kaoru Shimokata

European Journal of Immunology　30　(4)　1182-1190　2000

DOI： 10.1002/(SICI)1521-4141(200004)30:4<1182::AID-IMMU1182>3.0.CO;2-H 　

ISSN： 0014-2980
IgEによるFcεRI発現上昇の機構とそれに伴うマスト細胞の短期記憶の形成

久保秀一, 松岡邦枝, 多屋長治, 北村ふじ子, 高井俊行, 米川博通, 烏山一

日本免疫学会総会・学術集会記録　30　41　2000
Stimulatory function of paired immunoglobulin-like receptor-A in mast cell line by associating with subunits common to Fc receptors Peer-reviewed

Masao Ono, Takae Yuasa, Chisei Ra, Toshiyuki Takai

Journal of Biological Chemistry　274　(42)　30288-30296　1999/10/15

DOI： 10.1074/jbc.274.42.30288 　

ISSN： 0021-9258
FcγRIIB欠損マウスにおけるGoodpasture症候群モデルの作製

中村晃, 湯浅貴恵, 氏家あづさ, 小野栄夫, 高井俊行, 貫和敏博

加齢医学研究所雑誌　51　(1)　37-38　1999/10
Publisher: 東北大学加齢医学研究所
ISSN： 1340-3397
Modulation of immunoglobulin (Ig)E-mediated systemic anaphylaxis by low- affinity Fc receptors for IgG Peer-reviewed

Azusa Ujike, Yoko Ishikawa, Masao Ono, Takae Yuasa, Tadashi Yoshino, Manabu Fukumoto, Jeffrey V. Ravetch, Toshiyuki Takai

Journal of Experimental Medicine　189　(10)　1573-1579　1999/05/17

DOI： 10.1084/jem.189.10.1573 　

ISSN： 0022-1007
Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors Peer-reviewed

Raphael Clynes, Jay S. Maizes, Rodolphe Guinamard, Masao Ono, Toshiyuki Takai, Jeffrey V. Ravetch

Journal of Experimental Medicine　189　(1)　179-185　1999/01/04

DOI： 10.1084/jem.189.1.179 　

ISSN： 0022-1007
Deletion of Fcγ receptor IIB renders H-2b mice susceptible to collagen-induced arthritis Peer-reviewed

Takae Yuasa, Satoshi Kubo, Tadashi Yoshino, Azusa Ujike, Kimio Matsumura, Masao Ono, Jeffrey V. Ravetch, Toshiyuki Takai

Journal of Experimental Medicine　189　(1)　187-194　1999/01/04

DOI： 10.1084/jem.189.1.187 　

ISSN： 0022-1007
108 マウス喘息モデルにおける抑制性レセプターFcγRIIbの役割

北村賢一, 武田勝行, 武田明子, 木村五郎, 谷本安, 片岡幹男, 原田実根, 高井俊行, 金廣有彦, Gelfand Eriwin W.

アレルギー　48　(8)　971-971　1999
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.48.971_4 　
107 Fcγ鎖欠損マウスを用いた喘息モデルの解析

武田勝行, 北村賢一, 武田明子, 木村五郎, 谷本安, 片岡幹男, 金廣有彦, Gelfand Erwin W., 高井俊行, 原田実根

アレルギー　48　(8)　971-971　1999
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.48.971_3 　
465 遺伝子欠損マウスを用いたFcγレセプターによる抗原提示機能の解析

石川陽子, 矢田あゆみ, 松村公男, 小野栄夫, 相場節也, 高井俊行

アレルギー　48　(8)　1061-1061　1999
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.48.1061_1 　
REGULATION OF ANAPHYLACTIC RESPONSES BY Fc RECEPTORS

Takai Toshiyuki

Japanese Journal of Allergology　48　(12)　1291-1295　1999
Publisher: Japanese Society of Allergology
DOI： 10.15036/arerugi.48.1291 　

ISSN： 0021-4884
4 Fcγレセプターによるアレルギーと自己免疫の制御 (15 アレルギーの動物モデル)

高井俊行

アレルギー　48　(8)　926-926　1999
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.48.926_1 　
Fcレセプターとアレルギー

高井俊行

アレルギー　48　(2)　181-181　1999
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.48.181_1 　
【NK細胞をめぐって】NK活性とキラー抑制レセプター

高井俊行, 小野栄夫, 乾匡範

臨床免疫　31　(1)　40-46　1999/01
Publisher: (有)科学評論社
ISSN： 0386-9695
Inhibitory and stimulatory functions of paired Ig-like receptor (PIR) family in RBL-2H3 cells Peer-reviewed

Yumi Yamashita, Masao Ono, Toshiyuki Takai

Journal of Immunology　161　(8)　4042-4047　1998/10/15

ISSN： 0022-1767
Regulation of murine hypersensitive responses by Fc receptors

TAKAI Toshiyuki, ONO Masao, UJIKE Azusa, YUASA Takae

Allergol. Int.　47　(2)　75-83　1998/06/01
Publisher: Japanese Society of Allergology
DOI： 10.2332/allergolint.47.75 　

ISSN： 1323-8930

More details Close

Humoral and cellular immune responses communicate with each other via Fc receptors (FcR) expressed on various hematopoietic cells. Recent studies on several FcR knockout mice demonstrated pivotal roles of an IgG/FcγR system in the regulation of immune responses and the onset of hypersensitivity. The γ subunit of FcR is an essential component of the complex and is required for both receptor assembly and signal transduction. FcR γ chain-deficient mice have lost the functional expression of FcεRI, FcγRI, and FcγRIII and are unable to mount several types of hypersensitive reactions, including the skin Arthus reaction. In contrast, FcγRII-deficient mice exhibit augmented humoral immune responses and IgG-mediated anaphylaxis reactions. Thus, the regulatory system of murine hypersensitive responses involves both positive and negative signaling through FcR. In B cells, FcγRIIb modulates membrane Ig-induced Ca²⁺ mobilization by inhibiting Ca²⁺ influx through phosphorylation of its immunoreceptor tyrosine-based inhibition motif and recruitment of cytoplasmic phosphatases. Elucidation of the detailed mechanisms of negative regulatory signaling in the inflammatory effector cells by FcγRIIb as well as several groups of potent inhibitory molecules expressed on such cells should be valuable in the development of novel therapeutic procedures for allergic disorders.
Requirement of SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 for paired immunoglobulin-like receptor B (PIR-B)-mediated inhibitory signal Peer-reviewed

Akito Maeda, Mari Kurosaki, Masao Ono, Toshiyuki Takai, Tomohiro Kurosaki

Journal of Experimental Medicine　187　(8)　1355-1360　1998/04

DOI： 10.1084/jem.187.8.1355 　

ISSN： 0022-1007
Association of tyrosine phosphatases SHP-1 and SHP-2, inositol 5- phosphatase SHIP with gp49B1, and chromosomal assignment of the gene Peer-reviewed

Asato Kuroiwa, Yumi Yamashita, Masanori Inui, Takae Yuasa, Masao Ono, Akira Nagabukuro, Yoichi Matsuda, Toshiyuki Takai

Journal of Biological Chemistry　273　(2)　1070-1074　1998/01/09

DOI： 10.1074/jbc.273.2.1070 　

ISSN： 0021-9258
Genomic structures and chromosomal location of p91, a novel murine regulatory receptor family Peer-reviewed

Yumi Yamashita, Daisuke Fukuta, Atsushi Tsuji, Akira Nagabukuro, Yoichi Matsuda, Yasuhiro Nishikawa, Yukiya Ohyama, Hitoshi Ohmori, Masao Ono, Toshiyuki Takai

Journal of Biochemistry　123　(2)　358-368　1998
Publisher: Oxford University Press
DOI： 10.1093/oxfordjournals.jbchem.a021945 　

ISSN： 0021-924X
Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis Peer-reviewed

Yusuke Suzuki, Isao Shirato, Ko Okumura, Jeffrey V. Ravetch, Toshiyuki Takai, Yasuhiko Tomino, Chisei Ra

Kidney International　54　(4)　1166-1174　1998
Publisher: Blackwell Publishing Inc.
DOI： 10.1046/j.1523-1755.1998.00108.x 　

ISSN： 0085-2538
Characterization of B Cells Expressing Recombination Activating Genes in Germinal Centers of Immunized Mouse Lymph Nodes Peer-reviewed

Masaki Hikida, Masaharu Mori, Teruyuki Kawabata, Toshiyuki Takai, Hitoshi Ohmori

Journal of Immunology　158　(6)　2509-2512　1997/03/15

ISSN： 0022-1767
Molecular cloning of a novel murine cell-surface glycoprotein homologous to killer cell inhibitory receptors Peer-reviewed

Keiko Hayami, Daisuke Fukuta, Yasuhiro Nishikawa, Yumi Yamashita, Masanori Inui, Yukiya Ohyama, Masaki Hikida, Hitoshi Ohmori, Toshiyuki Takai

Journal of Biological Chemistry　272　(11)　7320-7327　1997/03/14

DOI： 10.1074/jbc.272.11.7320 　

ISSN： 0021-9258
512 マウスマスト細胞におけるFcγRIIとFcγRIIIの発現

熱田了, 鈴木勝宏, 松田浩則, 奥村康, 高井俊行, 羅智靖

アレルギー　46　(8)　944-944　1997
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.46.944_4 　
Reexpression of RAG-1 and RAG-2 genes in activated mature mouse B cells Peer-reviewed

Masaki Hikida, Masaharu Mori, Toshiyuki Takai, Ken-Ichi Tomochika, Kiyohiro Hamatani, Hitoshi Ohmori

Science　274　(5295)　2092-2094　1996/12/20

DOI： 10.1126/science.274.5295.2092 　

ISSN： 0036-8075
Suppression of in vitro cellular immune response by nitrogen-containing terpene alcohol derivatives Peer-reviewed

Y Okada, N Matono, M Shiono, T Takai, M Hikida, H Ohmori

BIOLOGICAL & PHARMACEUTICAL BULLETIN　19　(11)　1443-1446　1996/11

DOI： 10.1248/bpb.19.1443 　

ISSN： 0918-6158
Requirements of a costimulus for IL-4-induced IgE class switching in murine B cells activated via antigen receptors: Effectiveness of 8-mercaptoguanosine Peer-reviewed

Masaki Hikida, Toshiyuki Takai, Hitoshi Ohmori

Journal of Immunology　156　(8)　2730-2736　1996/04/15

ISSN： 0022-1767
Augmented humoral and anaphylactic responses in FcγRII-deficient mice Peer-reviewed

Toshiyuki Takai, Masao Ono, Masaki Hikida, Hitoshi Ohmori, Jeffrey V. Ravetch

Nature　379　(6563)　346-349　1996/01/25

DOI： 10.1038/379346a0 　

ISSN： 0028-0836
4. FCRγ鎖ノックアウトマウスによるアレルギー発症のメカニズム (<シンポジウム>2 アレルギーとFcレセプター)

高井俊行

アレルギー　45　(8)　804-804　1996
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.45.804_1 　
Multiple loss of effector cell functions in FcRγ-deficient mice Peer-reviewed

Toshiyuki Takai

International Reviews of Immunology　13　(4)　369-381　1996
Publisher: Informa Healthcare
DOI： 10.3109/08830189609061759 　

ISSN： 0883-0185
Induction of antigen-specific IgE response in murine lymphocytes by IL-10 Peer-reviewed

Hitoshi Ohmori, Tsutomu Kanda, Toshiyuki Takai, Masaki Hikida

Immunology Letters　47　(1-2)　127-132　1995

DOI： 10.1016/0165-2478(95)00084-I 　

ISSN： 0165-2478
5-Azacytidine enhances transient expression of a transfected gene in cultured mammalian cells Peer-reviewed

Toshiyuki Takai, Tatsuji Yasuda, Hitoshi Ohmori

Journal of Fermentation and Bioengineering　79　(6)　617-619　1995

DOI： 10.1016/0922-338X(95)94758-J 　

ISSN： 0922-338X
Enhancement of transgene expression in mammalian cell line by a Δ7-prostaglandin A1 analogue Peer-reviewed

Taichi Matsuda, Toshiyuki Takai, Masaki Hikida, Tatsuji Yasuda, Seizi Kurozumi, Hitoshi Ohmori

Journal of Fermentation and Bioengineering　79　(3)　281-283　1995

DOI： 10.1016/0922-338X(95)90617-9 　

ISSN： 0922-338X
Phorbol Ester-Induced Reversible Inactivation of Cytotoxic T Cell Function: Correlation with Down-Regulation of Protein Kinase C Activity Peer-reviewed

Hitoshi Ohmori, Toshitaka Shimada, Masaki Hikida, Toshiyuki Takai

Japanese Journal of Pharmacology　66　(4)　427-432　1994

DOI： 10.1254/jjp.66.427 　

ISSN： 0021-5198
Predominant suppression of anti-TNP IgE response in mice by monoclonal anti-TNP IgG1 antibody: characterization of its mode of action by in vitro and in vivo studies Peer-reviewed

Naoki Hase, Toshiyuki Takai, Masaki Hikida, Hitoshi Ohmori

International Journal of Immunopharmacology　16　(10)　787-794　1994

DOI： 10.1016/0192-0561(94)90052-3 　

ISSN： 0192-0561
Enzyme release assay of human NK cell activity using β-galactosidase-expressing K562 target cell line Peer-reviewed

Hitoshi Ohmori, Hidenori Ikeda, Takahiro Tanigawa, Toshiyuki Takai, Masaki Hikida

Journal of Immunological Methods　164　(1)　131-135　1993/08/26

DOI： 10.1016/0022-1759(93)90283-D 　

ISSN： 0022-1759
Enhancement of expression of an introduced gene by 5-azacytidine in mammalian cell lines Peer-reviewed

Takahiro Tanigawa, Masaki Hikida, Toshiyuki Takai, Tatsuji Yasuda, Hitoshi Ohmori

Journal of Fermentation and Bioengineering　75　(4)　254-258　1993

DOI： 10.1016/0922-338X(93)90147-Z 　

ISSN： 0922-338X
Enhancement of expression of introduced β-galactosidase gene by 2-aminopurine in mammalian cell lines Peer-reviewed

Takahiro Tanigawa, Masaki Hikida, Toshiyuki Takai, Hitoshi Ohmori

Journal of Fermentation and Bioengineering　76　(2)　145-147　1993

DOI： 10.1016/0922-338X(93)90072-G 　

ISSN： 0922-338X
Enhancement of DNA transfection efficiency by heat treatment of cultured mammalian cells Peer-reviewed

Toshiyuki Takai, Hitoshi Ohmori

BBA - Gene Structure and Expression　1129　(2)　161-165　1992/01/06

DOI： 10.1016/0167-4781(92)90481-E 　

ISSN： 0167-4781
Enhancement of antigen-induced interleukin 4 and IgE production by specific IgG1 in murine lymphocytes Peer-reviewed

Hitoshi Ohmori, Naoki Hase, Masaki Hikida, Toshiyuki Takai, Noriaki Endo

Cellular Immunology　145　(2)　299-310　1992

DOI： 10.1016/0008-8749(92)90333-K 　

ISSN： 1090-2163 0008-8749
Selective regulation of antigen-specific IgE response by cyclic AMP level in murine lymphocytes Peer-reviewed

Masaki Hikida, Toshiyuki Takai, Hitoshi Ohmori

Immunology Letters　33　(3)　301-306　1992

DOI： 10.1016/0165-2478(92)90077-2 　

ISSN： 0165-2478
Establishment of an enzyme release assay for cytotoxic T lymphocyte activity Peer-reviewed

Hitoshi Ohmori, Toshiyuki Takai, Takahiro Tanigawa, Yoichi Honma

Journal of Immunological Methods　147　(1)　119-124　1992

DOI： 10.1016/S0022-1759(12)80036-6 　

ISSN： 0022-1759
Regulation of prostaglandin E2 synthesis by cyclooxygenase induction in osteoblast MC3T3-E1 Peer-reviewed

Shozo Yamamoto, Takeo Oshima, Tanihiro Yoshimoto, Chieko Yokoyama, Toshiyuki Takai, Tadashi Tanabe, Masayoshi Kumegawa

Journal of Bone and Mineral Metabolism　9　(2)　45-48　1991/08
Publisher: Springer-Verlag
DOI： 10.1007/BF02377985 　

ISSN： 0914-8779 1435-5604
DNA transfection of mouse lymphoid cells by the combination of DEAE-dextran-mediated DNA uptake and osmotic shock procedure Peer-reviewed

Toshiyuki Takai, Hitoshi Ohmori

BBA - Gene Structure and Expression　1048　(1)　105-109　1990/01/30

DOI： 10.1016/0167-4781(90)90029-2 　

ISSN： 0167-4781
Highly efficient DNA transfection of hematopoietic cell lines by an improved DEAE-dextran method: A synergistic enhancement by hypertonic treatment and dimethyl sulfoxide

T. Takai, H. Ohmori

Methods in Molecular and Cellular Biology　2　(2)　82-90　1990

ISSN： 0898-7750
Cloning and sequence analysis of the cDNA for arachidonate 12-lipoxygenase of porcine leukocytes Peer-reviewed

T. Yoshimoto, H. Suzuki, S. Yamamoto, T. Takai, C. Yokoyama, T. Tanabe

Proceedings of the National Academy of Sciences of the United States of America　87　(6)　2142-2146　1990

DOI： 10.1073/pnas.87.6.2142 　

ISSN： 0027-8424
Prostaglandin E2 as a selective stimulator of antigen‐specific IgE response in murine lymphocytes Peer-reviewed

Hitoshi Ohmori, Masaki Hikida, Toshiyuki Takai

European Journal of Immunology　20　(11)　2499-2503　1990

DOI： 10.1002/eji.1830201121 　

ISSN： 1521-4141 0014-2980
Cytidylate cyclase activity in mouse tissues: the enzymatic conversion of cytidine 5′-triphosphate to cytidine 3′,5′-cyclic monophosphate (cyclic CMP) Peer-reviewed

Itaru Yamamoto, Toshiyuki Takai, Shuji Mori

BBA - General Subjects　993　(2-3)　191-198　1989/12/08

DOI： 10.1016/0304-4165(89)90163-3 　

ISSN： 0304-4165
Developmental changes of the content of acetyl-CoA carboxylase mRNA in chicken liver Peer-reviewed

Toshiyuki Takai, Yoko Saito, Kazuhiko Yamamoto, Tadashi Tanabe

Archives of Biochemistry and Biophysics　266　(2)　313-318　1988/11/01

DOI： 10.1016/0003-9861(88)90263-9 　

ISSN： 1096-0384 0003-9861
Primary structure of sheep prostaglandin endoperoxide synthase deduced from cDNA sequence Peer-reviewed

Chieko Yokoyama, Toshiyuki Takai, Tadashi Tanabe

FEBS Letters　231　(2)　347-351　1988/04/25

DOI： 10.1016/0014-5793(88)80847-0 　

ISSN： 0014-5793
Primary structure of chicken liver acetyl-CoA carboxylase deduced from cDNA sequence Peer-reviewed

T. Takai, C. Yokoyama, K. Wada, T. Tanabe

Journal of Biological Chemistry　263　(6)　2651-2657　1988

ISSN： 0021-9258
Primary structure of the biotin-binding site of chicken liver acetyl-CoA carboxylase Peer-reviewed

Toshiyuki Takai, Kenji Wada, Tadashi Tanabe

FEBS Letters　212　(1)　98-102　1987/02/09

DOI： 10.1016/0014-5793(87)81564-8 　

ISSN： 0014-5793
Amino acid sequence of chicken liver cathepsin L Peer-reviewed

Kenji WADA, Toshiyuki TAKAI, Tadashi TANABE

European Journal of Biochemistry　167　(1)　13-18　1987

DOI： 10.1111/j.1432-1033.1987.tb13298.x 　

ISSN： 1432-1033 0014-2956
Erratum: Molecular distinction between fetal and adult forms of muscle acetylcholine receptor (Nature (1986) 321 (406-411))

M. Mishina, T. Takai, K. Imoto, M. Noda, T. Takahashi, S. Numa, C. Methfessel, B. Sakmann

Nature　322　90　1986/12/01

DOI： 10.1038/322090a0 　

ISSN： 0028-0836
Molecular distinction between fetal and adult forms of muscle acetylcholine receptor Peer-reviewed

Masayoshi Mishina, Toshiyuki Takai, Keiji Imoto, Masaharu Noda, Tomoyuki Takahashi, Shosaku Numa, Christoph Methfessel, Bert Sakmann

Nature　321　(6068)　406-411　1986

DOI： 10.1038/321406a0 　

ISSN： 0028-0836
Role of acetylcholine receptor subunits in gating of the channel Peer-reviewed

Bert Sakmann, Christoph Methfessel, Masayoshi Mishina, Tomoyuki Takahashi, Toshiyuki Takai, Masaaki Kurasaki, Kazuhiko Fukuda, Shosaku Numa

Nature　318　(6046)　538-543　1985

DOI： 10.1038/318538a0 　

ISSN： 0028-0836
Cloning, sequencing and expression of cDNA for a novel subunit of acetylcholine receptor from calf muscle Peer-reviewed

Toshiyuki Takai, Masaharu Noda, Masayoshi Mishina, Shin Shimizu, Yasuji Furutani, Toshiaki Kayano, Takayuki Ikeda, Tai Kubo, Hideo Takahashi, Tomoyuki Takahashi, Motoy Kuno, Shosaku Numa

Nature　315　(6022)　761-764　1985

DOI： 10.1038/315761a0 　

ISSN： 0028-0836
Primary structure of δ subunit precursor of calf muscle acetylcholine receptor deduced from cDNA sequence Peer-reviewed

Tai KUBO, Masaharu NODA, Toshiyuki TAKAI, Tsutomu TANABE, Toshiaki KAYANO, Shin SHIMIZU, Ken‐ichi TANAKA, Hideo TAKAHASHI, Tadaaki HIROSE, Seiichi INAYAMA, Reiko KIKUNO, Takashi MIYATA, Shosaku NUMA

European Journal of Biochemistry　149　(1)　5-13　1985

DOI： 10.1111/j.1432-1033.1985.tb08885.x 　

ISSN： 1432-1033 0014-2956
Primary structure of β subunit precursor of calf muscle acetylcholine receptor deduced from cDNA sequence Peer-reviewed

Tsutomu TANABE, Masaharu NODA, Yasuji FURUTANI, Toshiyuki TAKAI, Hideo TAKAHASHI, Ken‐ichi TANAKA, Tadaaki HIROSE, Seiichi INAYAMA, Shosaku NUMA

European Journal of Biochemistry　144　(1)　11-17　1984

DOI： 10.1111/j.1432-1033.1984.tb08424.x 　

ISSN： 1432-1033 0014-2956
Primary structure of γ subunit precursor of calf‐muscle acetylcholine receptor deduced from the cDNA sequence Peer-reviewed

Toshiyuki TAKAI, Masaharu NODA, Yasuji FURUTANI, Hideo TAKAHASHI, Mitsue NOTAKE, Shin SHIMIZU, Toshiaki KAYANO, Tsutomu TANABE, Ken‐ichi TANAKA, Tadaaki HIROSE, Seiichi INAYAMA, Shosaku NUMA

European Journal of Biochemistry　143　(1)　109-115　1984

DOI： 10.1111/j.1432-1033.1984.tb08348.x 　

ISSN： 1432-1033 0014-2956
Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence Peer-reviewed

Masaharu Noda, Shin Shimizu, Tsutomu Tanabe, Toshiyuki Takai, Toshiaki Kayano, Takayuki Ikeda, Hideo Takahashi, Hitoshi Nakayama, Yuichi Kanaoka, Naoto Minamino, Kenji Kangawa, Hisayuki Matsuo, Michael A. Raftery, Tadaaki Hirose, Seiichi Inayama, Hidenori Hayashida, Takashi Miyata, Shosaku Numa

Nature　312　(5990)　121-127　1984

DOI： 10.1038/312121a0 　

ISSN： 0028-0836
Isolation and structural organization of the human preproenkephalin Bgene Peer-reviewed

Saburo Horikawa, Toshiyuki Takai, Mitsuyoshi Toyosato, Hideo Takahashi, Masaharu Noda, Hitoshi Kakidani, Tai Kubo, Tadaaki Hirose, Seiichi Inayama, Hidenori Hayashida, Takashi Miyata, Shosaku Numa

Nature　306　(5943)　611-614　1983

DOI： 10.1038/306611a0 　

ISSN： 0028-0836
Enzyme immunoassay for cytidine 3′,5′-cyclic monophosphate (cyclic CMP) Peer-reviewed

Itaru Yamamoto, Toshiyuki Takai, Jun-ichi Tsuji

Immunopharmacology　4　(4)　331-340　1982

DOI： 10.1016/0162-3109(82)90054-6 　

ISSN： 0162-3109

Show all ︎Show first 5

Misc. 131

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高鳥翔, 井口明優, 木村新伍, 堀由起子, 佐々木純子, 斉藤貴志, 西道隆臣, 池津庸哉, 高井俊行, 佐々木雄彦, 富田泰輔

Dementia Japan　35　(4)　595-595　2021/10
Publisher: (一社)日本認知症学会
ISSN： 1342-646X
Roles of inhibitory Fc receptor FcgammaRIIB on the peripheral B cell tolerance

NISHIMURA Hiroyuki, IIDA Noriko, OHTSUJI Mareki, KODERA Yo, TAKAI Toshiyuki, SUDO Katsuko, VERBEEK Sjef, HIROSE Sachiko

日本免疫学会総会・学術集会記録(CD-ROM)　50　2021

ISSN： 0919-1984
Fcγレセプター，抑制性レセプター Invited Peer-reviewed

遠藤章太, 蘇美慈, 高井俊行

臨床免疫・アレルギー科　73　(1)　43-50　2020/01
Immune regulation by PirB/LILRB2 and gp49B/LILRB4 Invited Peer-reviewed

Endo S, Su MT, Takai T

Seitai no Kagaku　70　(3)　223-229　2019/06
Epistatic interaction between Fcgr2b and Slam family genes in susceptibility to the defective peripheral immune tolerance and autoimmunity

NISHIMURA Hiroyuki, IIDA Noriko, OHTSUJI Mareki, KODERA Yo, TAKAI Toshiyuki, SUDO Katsuko, VERBEEK Sjef J, HIROSE Sachiko

日本免疫学会総会・学術集会記録(CD-ROM)　48　2019

ISSN： 0919-1984
脳内インフラストラクチャー: 脳細胞社会の恒常性維持機構と物流システムを担う機能的構造体アルツハイマー病遺伝学的リスク因子INPP5Dの病態関与に関する研究

高鳥翔, 井口明優, 木村新伍, 佐々木純子, 佐々木雄彦, 高井俊行, 斉藤貴志, 西道隆臣, 富田泰輔

日本生化学会大会プログラム・講演要旨集　92nd　[1S17m-05]　2019
Publisher: (公社)日本生化学会
アルツハイマー病リスク遺伝子INPP5DがTREM2シグナル伝達において果たす役割の解明

井口明優, 高鳥翔, 木村新伍, 佐々木純子, 斉藤貴志, 西道隆臣, 高井俊行, 佐々木雄彦, 富田泰輔

Dementia Japan　33　(4)　551-551　2019
Publisher: (一社)日本認知症学会
ISSN： 1342-646X
Epistatic interaction between fcgr2b and Slam family genes in susceptibility to defective foreign protein-induced tolerance

NISHIMURA Hiroyuki, OBATA Masaomi, OHTSUJI Mareki, KODERA Yo, TAKAI Toshiyuki, SUDO Katsuko, VERBEEK J. Sjef, HIROSE Sachiko

日本免疫学会総会・学術集会記録(CD-ROM)　47　2018

ISSN： 0919-1984
Epistatic interaction between fcgr2b and Slam family genes in susceptibility to defective foreign protein-induced tolerance

NISHIMURA Hiroyuki, OBATA Masaomi, OHTSUJI Mareki, KODERA Yo, TAKAI Toshiyuki, SUDO Katsuko, HIROSE Sachiko

日本免疫学会総会・学術集会記録(CD-ROM)　46　2017

ISSN： 0919-1984
Epistatic interaciton between fcgr2b and Slam family genes in susceptibility to defective foreign protein induced tolerance

NISHIMURA Hiroyuki, FUJII Takuma, OBATA Masaomi, OHTSUJI Mareki, KODERA Yo, TAKAI Toshiyuki, SUDO Katsuko, HIROSE Sachiko

日本免疫学会総会・学術集会記録　45　(Proceedings)　2016

ISSN： 0919-1984
[Ligand recognition and immune regulation system of inhibitory receptor PIR-B]. Invited Peer-reviewed

Endo S, Takai T

Seikagaku. The Journal of Japanese Biochemical Society　86　(5)　662-665　2014/10
Publisher: 日本生化学会
ISSN： 0037-1017
Regulation of inflammatory responses by PIR-B Invited Peer-reviewed

60　(5)　486-491　2013
Publisher: 科学評論社
ISSN： 1881-1930
[Regulation of osteoclast development by immunoglobulin-like receptors].

Masanori Inui, Toshiyuki Takai

Clinical calcium　22　(11)　1651-1657　2012

ISSN： 0917-5857
Fc gamma receptor targeting in RA

Toshiyuki Takai, Akira Nakamura, Akiko Tobinai, Shota Endo, Masanori Inui

ARTHRITIS RESEARCH & THERAPY　14　2012

ISSN： 1478-6354
B細胞におけるPIR-Bの発現制御転写因子. Invited Peer-reviewed

北口公司, 遠藤章太, 高井俊行

臨床免疫・アレルギー科　57　500-505　2012
Paired immunoglobulin-like receptor(PIR)-Bの自己免疫疾患における役割

中村晃, 高井俊行

リウマチ科　46　(2)　184-189　2011/08
Publisher: (有)科学評論社
ISSN： 0915-227X
Presumptive role of 129 strain-derived Sle16 locus for rheumatoid arthritis in a new mouse model with Fc γ RIIB-deficient C57BL/6 genetic background

SATO Aya, OHTSUJI Mareki, LIN Qingshun, OHTSUJI Naomi, NISHIKAWA Keiko, TSURUI Hiromichi, ONO Masao, SHIRAI Toshikazu, TAKAI Toshiyuki, NISHIMURA Hiroyuki, HIROSE Sachiko

日本免疫学会総会・学術集会記録　40　2011

ISSN： 0919-1984
骨髄球系細胞におけるMDL-1/DAP12の機能. Invited Peer-reviewed

北口公司, 遠藤章太, 乾匡範, 高井俊行

リウマチ科　45　(5)　531-535　2011
Publisher: (有)科学評論社
ISSN： 0915-227X
Presumptive role of 129 strain-derived Sle16 locus in rheumatoid arthritis in a new mouse model with Fcgamma receptor type IIb-deficient C57BL/6 genetic background.

Sato-Hayashizaki Aya, Ohtsuji Mareki, Lin Qingshun, Hou Rong, Ohtsuji Naomi, Nishikawa Keiko, Tsurui Hiromichi, Sudo Katsuko, Ono Masao, Izui Shozo, Shirai Toshikazu, Takai Toshiyuki, Nishimura Hiroyuki, Hirose Sachiko

Arthritis Rheum　63　(10)　2930-2938　2011

DOI： 10.1002/art.30485 　

ISSN： 0004-3591

eISSN： 1529-0131
【アレルギーの感作と発症】免疫抑制性レセプターPIR-Bによるアレルギー制御

北口公司, 中村晃, 高井俊行

臨床免疫・アレルギー科　54　(5)　540-545　2010/11
Publisher: (有)科学評論社
ISSN： 1881-1930
PIR-BによるNogo/MHCクラスI認識の相違性に基づくマスト細胞の新しい制御機構

遠藤章太, 北口公司, 中村晃, 高井俊行

アレルギー　59　(9-10)　1428-1428　2010/10
Publisher: (一社)日本アレルギー学会
ISSN： 0021-4884

eISSN： 1347-7935
炎症とDAP12/DAP10/FcRγ

中村晃, 乾匡範, 高井俊行

感染・炎症・免疫　40　(2)　120-129　2010/07
Publisher: 鳥居薬品(株)
ISSN： 0387-1010
【B細胞の分化・生存・機能制御の分子機能】 PIR-B、CD22、CD72からのシグナルによるB細胞活性化抑制の機序

中村晃, 高井俊行

臨床免疫・アレルギー科　54　(1)　35-43　2010/07
Publisher: (有)科学評論社
ISSN： 1881-1930
Genetic deletion of paired immunoglobulin-like receptor B does not promote axonal plasticity or functional recovery after traumatic brain injury

Shusaku Omoto, Masaki Ueno, Soichiro Mochio, Toshiyuki Takai, Toshihide Yamashita

NEUROSCIENCE RESEARCH　68　E254-E254　2010

DOI： 10.1016/j.neures.2010.07.1126 　

ISSN： 0168-0102
Paired immunoglobulin-like receptor B knockout does not enhance axonalregeneration or locomotor recovery after spinal cord injury

Yuka Nakamura, Yuki Fujita, Masaki Ueno, Toshiyuki Takai, Toshihide Yamashita

NEUROSCIENCE RESEARCH　68　E254-E254　2010

DOI： 10.1016/j.neures.2010.07.1125 　

ISSN： 0168-0102
【アレルギー疾患の免疫機構免疫細胞・サイトカインからみたアレルギー発症機序と治療へ向けた臨床的アプローチ】アレルギー疾患の基礎研究アレルギー疾患に関連する免疫細胞群受容体による肥満細胞の活性化制御

中村晃, 高井俊行

実験医学　27　(20)　3259-3263　2009/12
Publisher: (株)羊土社
ISSN： 0288-5514
The study of allergy by Japanese researchers: a historical perspective

Toshiyuki Takai, Hajime Karasuyama

INTERNATIONAL IMMUNOLOGY　21　(12)　1311-1316　2009/12

DOI： 10.1093/intimm/dxp105 　

ISSN： 0953-8178

eISSN： 1460-2377
Ectopically expressed PIR‐B on T cells constitutively binds to MHC class I cis and attenuates T helper type 1 responses.

IMADA Michiyo, MASUDA Kyoko, SATOH Rumi, ITO Yumi, GOTOH Yoshiyuki, MATSUOKA Takayuki, ENDO Shota, NAKAMURA Akira, KAWAMOTO Hiroshi, TAKAI Toshiyuki

日本免疫学会総会・学術集会記録　39　236　2009/11/10

ISSN： 0919-1984
アレルギーの感作成立=発症なのか? 免疫抑制性レセプターPIR-Bによるアレルギー制御

高井俊行, 中村晃

アレルギー　58　(8-9)　1132-1132　2009/09
Publisher: (一社)日本アレルギー学会
ISSN： 0021-4884

eISSN： 1347-7935
【感染現象その理解の深化から疾患制御への展望】生体防御機構研究の新展開 PIRによる新規CTL活性調節システム

遠藤章太, 中村晃, 高井俊行

蛋白質・核酸・酵素　54　(8)　1108-1113　2009/06
Publisher: 共立出版(株)
ISSN： 0039-9450
破骨細胞分化における免疫受容体会合性シグナルアダプター分子DAP10の重要性

藤村紫音, 乾匡範, 菊地佑樹, 青木直子, 遠藤章太, 前田努, 飛内章子, 原, 中村晃, 熊ノ郷淳, Colonna Marco, 高井俊行

Clinical Calcium　19　(6)　860-860　2009/05
Publisher: (株)医薬ジャーナル社
ISSN： 0917-5857
【自己免疫の発生に関与する要因】自己免疫の発生とPIR-B

中村晃, 窪智宏, 高井俊行

臨床免疫・アレルギー科　51　(4)　325-330　2009/04
Publisher: (有)科学評論社
ISSN： 1881-1930
Fc受容体と自己免疫

中村晃, 高井俊行

リウマチ科　41　(2)　214-221　2009/02
Publisher: (有)科学評論社
ISSN： 0915-227X
LMIR3 transmits both an inhibitory signal via ITIM in the cytoplasmic region and an activating signal by associating with ITAM‐containing FcRgamma in mast cells.

IZAWA Kumi, KITAURA Jiro, YAMANISHI Yoshinori, MATSUOKA Takayuki, OKI Toshihiko, TAKAI Toshiyuki, KITAMURA Toshio

日本免疫学会総会・学術集会記録　38　253　2008/11/05

ISSN： 0919-1984
【シグナル伝達研究 2008'09 疾患発症の分子メカニズムと実現化する分子標的薬開発】シグナル伝達研究現象から因子へ PIRシグナルと免疫疾患

高井俊行, 中村晃, 遠藤章太

実験医学　26　(15)　2411-2417　2008/09
Publisher: (株)羊土社
ISSN： 0288-5514
Inhibitory MHC class I receptors on myeloid cells

Akira Nakamura, Toshiyuki Takai

Current Immunology Reviews　4　(2)　80-87　2008/05

DOI： 10.2174/157339508784325082 　

ISSN： 1573-3955
Mucosal CD11b+DCs were Increased in PIRB Knockout Mice

Ryoki Kobayashi, Hiromi Kubagawa, Toshiyuki Takai, Shinichi Sekine, Jerry R. McGhee, Kohtaro Fujihashi

FASEB JOURNAL　22　2008/04

ISSN： 0892-6638
キラーT細胞のはたらきを調節する受容体分子を発見． Invited Peer-reviewed

遠藤章太, 高井俊行

Medical Bio　5　(6)　12-13　2008
Functional analysis of an inhibitory reseptor LMIR3 and an activating receptor LMIR4

IZAWA Kumi, KITAURA Jiro, YAMANISHI Yoshinori, MATSUOKA Takayuki, OKI Yoshihiko, TAKAI Toshiyuki, KITAMURA Toshio

日本免疫学会総会・学術集会記録　37　197　2007/10/25

ISSN： 0919-1984
Analysis of mouse LMIR5/CLM7 as an activating receptor: differential regulation of LMIR5/CLM7 in mouse verus human cells.

YAMANISHI Yoshinori, KITAURA Jiro, IZAWA Kumi, MATSUOKA Takayuki, OKI Toshihiko, TAKAI Toshiyuki, KITAMURA Toshio

日本免疫学会総会・学術集会記録　37　197　2007/10/25

ISSN： 0919-1984
Fc receptors: their diverse functions in immunity and immune disorders. (Springer Semin Immunopathol)

Takai Toshiyuki

Springer Semin Immunopathol　28　(4)　303-304　2006/12

DOI： 10.1007/s00281-006-0055-y 　
The characterization of a novel immunoglobulin‐like receptor, leukocyte mono‐Ig‐like receptor 5 (LMIR5)

YAMANISHI Yoshinori, KITAURA Jiro, IZAWA Kumi, MATSUOKA Takayuki, OKI Toshihiko, TAKAI Toshiyuki, KITAMURA Toshio

日本免疫学会総会・学術集会記録　36　256　2006/11/15

ISSN： 0919-1984
Charachterization of LMIR4, an activating receptor, which could pair with LMIR3, an inhibitory receptor

IZAWA Kumi, KITAURA Jiro, YAMANISHI Yoshinori, OKI Toshihiko, MATSUOKA Takayuki, TAKAI Toshiyuki, KITAMURA Toshio

日本免疫学会総会・学術集会記録　36　151　2006/11/15

ISSN： 0919-1984
活性化CD200レセプターを介したNK細胞の新たな腫瘍細胞認識機構

佐藤毅史, 石川哲, 白鳥行大, 荒瀬規子, 高井俊行, Lanier Lewis L, 荒瀬尚

日本癌学会総会記事　65回　457-458　2006/09
Publisher: 日本癌学会
ISSN： 0546-0476
Enhanced mucosal IgA ab responses in PIR-B knockout mice

Ryoki Kobayashi, H. Kubagawa, T. Takai, S. Sekine, Jerry R. McGhee, K. Fujihashi

JOURNAL OF IMMUNOLOGY　176　S244-S244　2006/04

ISSN： 0022-1767
Regulatory mechanisms of osteoclast development and bone disorders

Masanori Inui, Y. Mori, Toshiyuki Takai

Seikagaku. The Journal of Japanese Biochemical Society.　78　(3)　250-256　2006/03/01

ISSN： 0037-1017
ジェネラルレビュー:樹状細胞とT細胞のインターフェイス (抗原認識,co-raceptor)

高井俊行

免疫　2006　70-76　2006
Publisher: 中山書店
ISSN： 0918-6557
抑制性MHCクラス1レセプターPIR-BによるGVHDの制御 (病気と免疫)

中村晃, 高井俊行

免疫　2006　318-324　2006
Publisher: 中山書店
ISSN： 0918-6557
PIR. Invited Peer-reviewed

遠藤章太, 高井俊行

分子細胞治療　5　372-373　2006
第三の自己認識セレプターPIR (臨床免疫)

中村晃, 高井俊行

臨床免疫　44　(6)　647-653　2005/12
Publisher: 科学評論社
ISSN： 0386-9695
NK細胞の活性化CD200レセプターを介した新たな標的細胞認識機構

石川哲, 白鳥行大, 荒瀬規子, 高井俊行, Lanier Lewis L, 荒瀬尚

日本免疫学会総会・学術集会記録　35　99-99　2005/11
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
IgGとアレルギー (アレルギー)

高井俊行

アレルギー　54　(10)　1183-1189　2005/10

DOI： 10.15036/arerugi.54.1183 　
Fcγレセプターによる免疫制御と疾患

高井俊行

耳鼻咽喉科免疫アレルギー　23　(2)　7-13　2005/09/30

ISSN： 0913-0691
Paired immunoglobulin-like receptors and their MHC class I recognition

T Takai

IMMUNOLOGY　115　(4)　433-440　2005/08

DOI： 10.1111/j.1365-2567.2005.02177.x 　

ISSN： 0019-2805
造血幹細胞移植の成否の鍵を握るペア型イムノグロブリン様受容体 : ドナー細胞によるレシピエントへの攻撃をいかに回避・コントロールするか

高井俊行

化学と生物　43　(7)　424-426　2005/07/01
Publisher: 日本農芸化学会
ISSN： 0453-073X
IgGとアレルギー (アレルギー)

高井俊行

アレルギー　54　(3〜4)　215-215　2005/04
Publisher: 一般社団法人日本アレルギー学会
DOI： 10.15036/arerugi.54.215 　
自己免疫性糖尿病モデルマウス(NOD)におけるFcレセプターの関与

井上吉浩, 中村晃, 高井俊行

加齢医学研究所雑誌　56　(2)　59-59　2005/02
Publisher: 東北大学加齢医学研究所
ISSN： 1340-3397
Fc receptor targeting in the treatment of allergy, autoimmune diseases and cancer

Akira Nakamura, Kenichi Akiyama, Toshiyuki Takai

Expert Opinion on Therapeutic Targets　9　(1)　169-190　2005/02

DOI： 10.1517/14728222.9.1.169 　

ISSN： 1472-8222
自己免疫の治療ターゲットとしてのFcγR2B (病気と免疫)

高井俊行, 中村晃

免疫　2005　385-392　2005
Publisher: 中山書店
ISSN： 0918-6557
Regulation of osteoclast development by immunoglobulin-like receptors

Toshiyuki Takai, Masanori Inui, Kazuya Inoue, Y. Mori

Nippon rinsho. Japanese journal of clinical medicine　63　(9)　1562-1568　2005/01/01

ISSN： 0047-1852
Fc receptors and their role in immune regulation and autoimmunity

T Takai

JOURNAL OF CLINICAL IMMUNOLOGY　25　(1)　1-18　2005/01

DOI： 10.1007/s10875-005-0353-8 　

ISSN： 0271-9142
A novel recognition system for MHC class I molecules constituted by PIR

T Takai

ADVANCES IN IMMUNOLOGY, VOL 88　88　161-192　2005

DOI： 10.1016/S0065-2776(05)88005-8 　

ISSN： 0065-2776
Sema6Dはplexin-A1を介して免疫細胞を活性化する

竹ヶ原宜子, 熊ノ郷淳, 山本みどり, 高松漂太, 識名崇, 丸川聡子, 石田勲, 高井俊行, 菊谷仁

日本免疫学会総会・学術集会記録　34　201-201　2004/11
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
アダプター分子DAP12およびFcRγを介するITAMシグナルは破骨細胞分化に必須である

乾匡範, 古賀貴子, 井上和也, 谷口維紹, 高柳広, 高井俊行

日本免疫学会総会・学術集会記録　34　231-231　2004/11
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
Fcレセプターと関節炎 Invited

後藤義幸, 中村晃, 高井俊行

分子リウマチ　1　(4)　50-56　2004/11
Paired immunoglobulin-like receptor(PIR)による移植片対宿主病(GVHD)の制御

中村晃, 小林栄治, 高井俊行

日本免疫学会総会・学術集会記録　34　148-148　2004/11
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
ITAM-mediated costimulatory signals cooperate with RANKL for osteoclastogenesis.

T Koga, M Inui, A Suematsu, T Taniguchi, T Takai, H Takayanagi

JOURNAL OF BONE AND MINERAL RESEARCH　19　S82-S82　2004/10

ISSN： 0884-0431
ITAMを介した共刺激シグナルはRANKLによる破骨細胞分化に必須である

古賀貴子, 乾匡範, 末松綾子, 谷口維紹, 高井俊行, 高柳広

日本骨代謝学会学術集会プログラム抄録集　22回　122-122　2004/08
Publisher: (一社)日本骨代謝学会
ISSN： 1349-0761
A role of Fc gamma RIIB in the development of collagen-induced arthritis

A Nakamura, T Takai

BIOMEDICINE & PHARMACOTHERAPY　58　(5)　292-298　2004/06

DOI： 10.1016/j.biopha.2004.04.005 　

ISSN： 0753-3322
免疫グロブリン様受容体(IgLR)分子群による免疫制御 (日本小児血液学会雑誌)

中村晃, 高井俊行

日本小児血液学会雑誌　18　(2)　59-68　2004/04

DOI： 10.11412/jjph1987.18.59 　
Defective ligation of PIR-B to MHC class I molecules leads to accelerated graft-versus-host disease (GVHD)

A Nakamura, E Kobayashi, T Takai

FASEB JOURNAL　18　(4)　A84-A84　2004/03

ISSN： 0892-6638
Augmented anaphylactic responses in PIR-B-deficient mice

A Masuda, T Maeda, A Nakamura, T Takai

FASEB JOURNAL　18　(5)　A792-A792　2004/03

ISSN： 0892-6638
PIR-B欠損マウスにおける移植片対宿主病の増悪

中村晃, 小林栄治, 高井俊行

加齢医学研究所雑誌　55　(1)　29-29　2004/03
Publisher: 東北大学加齢医学研究所
ISSN： 1340-3397
自己免疫疾患におけるFcγレセプターの役割 (臨床免疫)

後藤義幸, 金田崇文, 高井俊行

臨床免疫　41　(2)　180-189　2004/02
Publisher: 科学評論社
ISSN： 0386-9695
Role of paired Ig-like receptor-B in the humoral immune response

Toshiyuki Takai

Allergology International　53　(2)　93-99　2004
Publisher: Blackwell Publishing
DOI： 10.1111/j.1440-1592.2004.00327.x 　

ISSN： 1323-8930
Antigen targeting to Fc gamma receptors on bone marrow-derived dendritic cells efficiently elicits humoral response and cytotoxic T lymphocytes in vivo

S Endo, K Akiyama, A Yada, S Ebihara, K Matsumura, T Maeda, A Nakamura, S Aiba, T Nukiwa, T Takai

JOURNAL OF INVESTIGATIVE DERMATOLOGY　121　(5)　1250-1250　2003/11

ISSN： 0022-202X
温度感受性SV40 Large T抗原トランスジェニックマウスからの株化マスト細胞の樹立ならびに機能解析

兼平雅彦, 伊藤梢, 伊藤由美, 中村晃, 高井俊行

日本免疫学会総会・学術集会記録　33　162-162　2003/11
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
Paired Immunoglobulin-like Receptor(PIR)-Bによるマスト細胞の恒常的抑制

前田努, 増田愛, 中村晃, 高井俊行

日本免疫学会総会・学術集会記録　33　158-158　2003/11
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
PIR-B欠損マウスにおけるI型アレルギーの亢進

高井俊行, 増田愛, 前田努, 小林栄治, 中村晃

アレルギー　52　(8-9)　765-765　2003/09
Publisher: (一社)日本アレルギー学会
DOI： 10.15036/arerugi.52.765_1 　

ISSN： 0021-4884
Fc receptors as potential targets for the treatment of allergy, autoimmune disease and cancer. (Curr Drug Targets Immune Endocr Metabol Disord)

Takai Toshiyuki, Nakamura Akira, Akiyama Kenichi

Curr Drug Targets Immune Endocr Metabol Disord　3　(3)　187-197　2003/09

DOI： 10.2174/1568008033340180 　
Fc gamma RIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease

K Yajima, A Nakamura, A Sugahara, T Takai

FASEB JOURNAL　17　(7)　C41-C41　2003/04

ISSN： 0892-6638
Paired Immunoglobulin-like Receptor(PIR)-B欠損マウスの解析

浅井あづさ, 氏家, 竹田和彦, 中村晃, 海老原伸, 秋山健一, 高井俊行

加齢医学研究所雑誌　54　(1〜2)　53-53　2003/03
Publisher: 東北大学加齢医学研究所
ISSN： 1340-3397
Fcレセプター欠損マウスにおける免疫異常 (免疫研究の最前線--高次複雑系免疫システムの包括的理解をめざして) -- (免疫疾患・異常とその制御)

高井俊行

蛋白質核酸酵素　47　(16)　2375-2381　2002/12
Publisher: 共立出版
ISSN： 0039-9450
話題マスト細胞活性化と過敏反応におけるLynキナーゼの役割

湯浅貴恵, 小野栄夫, 高井俊行

臨床免疫　37　(5)　567-572　2002/05
Publisher: 科学評論社
ISSN： 0386-9695
Hypersensitive B cells and Th2-prone immune responses in paired immunoglobulin-like receptor (PIR)-B-deficient mice.

T Takai, A Ujike, K Takeda, A Nakamura, S Ebihara, K Akiyama

FASEB JOURNAL　16　(4)　A313-A313　2002/03

ISSN： 0892-6638
【知っておきたい200words 現代医学理解のために】抑制性Fc受容体

中村晃, 高井俊行

医学のあゆみ　200　(13)　1273-1273　2002/03
Publisher: 医歯薬出版(株)
ISSN： 0039-2359
【免疫疾患 state of arts】病態に関する基礎的研究の進歩 Fcレセプター欠損マウス

中村晃, 高井俊行

医学のあゆみ　別冊　(免疫疾患-state of arts Ver.2)　307-310　2002/03
Publisher: 医歯薬出版(株)
ISSN： 0039-2359
免疫疾患とその動物モデル関節炎の発症におけるFcレセプターの役割

中村晃, 矢島佳央里, 高井俊行

日本臨床免疫学会会誌　25　(1)　56-61　2002/02
Publisher: 日本臨床免疫学会
DOI： 10.2177/jsci.25.56 　

ISSN： 0911-4300
DAP12遺伝子欠損マウスにおける骨形成異常の解析

乾匡範, 海部知則, 金沢潔, 鍛冶光司, 菅原章子, 中村晃, 工藤明, 高井俊行

日本免疫学会総会・学術集会記録　32　2002

ISSN： 0919-1984
Secretory leukoprotease inhibitor(SLPI)遺伝子欠損マウスはLPSによるendotoxin shockに高感受性である

中村晃, 森ゆり子, 萩原弘一, 鈴木拓児, 菊地利明, 海老名雅仁, 阿部達也, 高井俊行, 貫和敏博

日本免疫学会総会・学術集会記録　32　126-126　2002
Publisher: (NPO)日本免疫学会
ISSN： 0919-1984
免疫疾患 Fcレセプター欠損マウスと免疫異常

中村晃, 貫和敏博, 高井俊行

Annual Review免疫　2002　283-289　2001/12
Publisher: (株)中外医学社
免疫疾患とその動物モデル関節炎の発症におけるFcレセプターの役割

高井俊行, 中村晃, 矢島佳央里

日本臨床免疫学会会誌　24　(5)　222-222　2001/10
Publisher: 日本臨床免疫学会
ISSN： 0911-4300
A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection

T Yoneto, S Waki, T Takai, Y Tagawa, Y Iwakura, J Mizuguchi, H Nariuchi, T Yoshimoto

JOURNAL OF IMMUNOLOGY　166　(10)　6236-6241　2001/05

ISSN： 0022-1767
RA疾患遺伝子候補Dblノックアウトマウスの作製

向江直子, 乾匡範, 駒井浩一郎, 小西良武, 高井俊行, 塩沢俊一

リウマチ　41　(2)　473-473　2001/04/17
Publisher: (一社)日本リウマチ学会
ISSN： 0300-9157
【慢性関節リウマチ遺伝子異常とその修復】遺伝子変異による疾患モデルマウス Fcγ受容体遺伝子欠損マウス

中村晃, 小野栄夫, 貫和敏博, 高井俊行

最新医学　56　(4)　871-876　2001/04
Publisher: (株)最新医学社
ISSN： 0370-8241
【アレルギーと慢性炎症の分子医学】炎症とFcレセプター

中村晃, 氏家あづさ, 小野栄夫, 貫和敏博, 高井俊行

Molecular Medicine　38　(5)　538-543　2001/04
Publisher: (株)中山書店
ISSN： 0918-6557
Functional association of CD9 with the Fc gamma receptors in macrophages

K Kaji, S Takeshita, K Miyake, T Takai, A Kudo

JOURNAL OF IMMUNOLOGY　166　(5)　3256-3265　2001/03

ISSN： 0022-1767
Fcγレセプターとアレルギー反応

氏家あづさ, 中村晃, 小野栄夫, 高井俊行

アレルギー科　11　(3)　268-274　2001/03
Publisher: (有)科学評論社
ISSN： 1341-7584
DAP12欠損マウスにおける前脳・視床中心性のオリゴデンドロサイト発達障害とゲート異常

海部知則, 乾匡範, 氏家あづさ, 高井俊行, 鍛冶光司, 中原仁, 竹内京子, 三島健一, 藤原道弘

日本神経科学大会プログラム・抄録集　24th　2001

ISSN： 1347-8583
DAP12欠損マウスにおける前脳・視床中心性のオリゴデンドロサイト発達障害とゲート異常

海部知則, 乾匡範, 氏家あづさ, 高井俊行, 鍛治光司, 中原仁, 阿相ひろ晃, 三島健一, 藤原道弘

神経化学　40　(2/3)　2001

ISSN： 0037-3796
Activating and inhibitory nature of the murine paired immunoglobulin-like receptor family

Toshiyuki Takai, Masao Ono

Immunological Reviews　181　215-222　2001

DOI： 10.1034/j.1600-065X.2001.1810118.x 　

ISSN： 0105-2896
Fc受容体による免疫抑制とその破綻

高井俊行

日本皮膚科学会雑誌　110　(12)　1801-1802　2000/11/15

ISSN： 0021-499X
【Fc受容体の基礎と臨床】 Fc受容体と自己免疫疾患モデルマウス

中村晃, 小野栄夫, 貫和敏博, 高井俊行

最新医学　55　(10)　2310-2315　2000/10
Publisher: (株)最新医学社
ISSN： 0370-8241
RAの疾患遺伝子候補DblホモログマウスMcf‐2 cDNAの単離

向江直子, 北川道憲, 駒井浩一郎, 小西良武, 乾匡範, 高井俊行, 塩沢俊一

リウマチ　40　(2)　416-416　2000/04/26
Publisher: (一社)日本リウマチ学会
ISSN： 0300-9157
Fc gamma receptor IIB-deficient mice develop Goodpasture's Syndrome upon immunization with type IV collagen.

T Takai, A Nakamura, T Yuasa, A Ujike, M Ono, T Nukiwa, JV Ravetch

FASEB JOURNAL　14　(6)　A994-A994　2000/04

ISSN： 0892-6638
Fc受容体による免疫抑制とその破綻

高井俊行

日本皮膚科学会雑誌 = THE JAPANESE JOURNAL OF DERMATOLOGY　110　(4)　534-536　2000/03/20

ISSN： 0021-499X
【アレルギー反応の機構をめぐって】マスト細胞の活性化とFcγレセプター

中村晃, 氏家あづさ, 石川陽子, 小野栄夫, 高井俊行

臨床免疫　33　(2)　149-153　2000/02
Publisher: (有)科学評論社
ISSN： 0386-9695
活性化・抑制の両者を制御するPIR (免疫系を調節する分子)

高井俊行, 小野栄夫

免疫　(1999)　46-54　1999/07
Publisher: 中山書店
ISSN： 0918-6557
Modulation of IGE-mediated systemic anaphylaxis by murine low affinity Fc receptors for IgG.

A Ujike, Y Ishikawa, M Ono, T Yuasa, T Yoshino, M Fukumoto, JV Ravetch, T Takai

FASEB JOURNAL　13　(4)　A324-A324　1999/03

DOI： 10.1084/jem.189.10.1573 　

ISSN： 0892-6638

eISSN： 1530-6860
Deletion of Fc gamma RIIB renders H-2(b) mice susceptible to collagen-induced arthritis.

T Yuasa, S Kubo, T Yoshino, A Ujike, K Matsumura, M Ono, JV Ravetch, T Takai

FASEB JOURNAL　13　(5)　A1120-A1120　1999/03

DOI： 10.1084/jem.189.1.187 　

ISSN： 0892-6638
Stimulatory function of Paired Immunoglobulin-like Receptor-A in mast cell line by associating with subunits comm on to Fc receptors

ONO Masao, YUASA Takae, RA Chisei, TAKAI Toshiyuki

21　185-185　1998/12/01
Generation and analysis of FcγRIII-deficient mice

ISHIKAWA Yoko, UJIKE Azusa, YUASA Takae, ONO Masao, TAKAI Toshiyuki

21　587-587　1998/12/01
Inhibitory function of paired immunoglobulin-like receptor-B(PIR-B)in RBL-2H3 cells

TAKEDA Kazuhiko, YAMASHITA Yumi, ONO Masao, TAKAI Toshiyuki

21　587-587　1998/12/01
Positive and Negative Immune Regulation via Fc Receptors

TAKAI T.

110　(2)　189-192　1998/12

ISSN： 0040-8700
Functional analysis of Fc receptors in hypersensitive responses by gene targeting.

Takai Toshiyuki

10　119-119　1998
Publisher: 日本生物工学会
Fcレセプタ-とアレルギ- (特集アレルギ-疾患の分子機構)

高井俊行, 小野栄夫

モレキュラ-メディシン　34　(12)　1464-1476　1997/12
Publisher: 中山書店
ISSN： 0918-6557
Fcレセプタ-と抗体産生制御

高井俊行

臨床免疫　29　(7)　898-904　1997/07
Publisher: 科学評論社
ISSN： 0386-9695
Immunoregulatory functions of Fc receptors

TAKAI Toshiyuki

69　(6)　394-409　1997/06/25
Publisher: 日本生化学会
ISSN： 0037-1017
Fcレセプタ-欠損マウス (特集 B細胞・免疫グロブリンと疾患)

高井俊行, 山下由美

モレキュラ-メディシン　34　(1)　44-54　1997/01
Publisher: 中山書店
ISSN： 0918-6557
Fcγレセプターによる免疫制御 (免疫生物学)

高井俊行

免疫　(1996)　144-153　1996/08
Publisher: 中山書店
ISSN： 0918-6557
Fc受容体ノックアウトマウスを用いた炎症反応の解析

高井俊行, 久保聡司, 疋田正喜, 大森斉, 羅智靖, 小野栄夫, RAVETCH Jeffrey v.

日本分子生物学会年会プログラム・講演要旨集　19　20-20　1996/08
8-メルカプトグアノシンによる抗原レセプター依存性のIgEクラススイッチ誘導機構の解析

疋田正喜, 高井俊行, 大森斉

日本分子生物学会年会プログラム・講演要旨集　19　342-342　1996/08/01
Isolation and analysis of B cell hybridoma that can undergo isotype switching to IgE by stimulation via antigen-receptor.

Hikida Masaki, Ueura Norichika, Takai Toshiyuki, Ohmori Hitoshi

8　26-26　1996
Publisher: 日本生物工学会
Generation and analysis of Fcy RII-deficient mice by gene targeting.

Ueura Norichika, Takai Toshiyuki, Kubo Satoshi, Hikida Masaki, Ohmori Hitoshi, Ono Masao, Ravetch J. V.

7　156-156　1995
Publisher: 日本生物工学会
Screening of novel immunosuppressive agents from fish enteric bacteria.

Raito Masayuki, Hikida Masaki, Takai Toshiyuki, Yazawa Kazunaga, Omori Hitoshi

7　156-156　1995
Publisher: 日本生物工学会
Isolation and charachterization of helper T cell subclones with different potencies to induce IgE response

Ujike Azusa, Hikida Masaki, Takai Toshiyuki, Ohmori Hitoshi

7　157-157　1995
Publisher: 日本生物工学会
Generation of FcγRII-deficient mouse by targeted disruption of the gene in ES cells.

Takai Toshiyuki, Hayami Keiko, Ohmori Hitoshi, Ravetch Jeffrey V.

6　241-241　1994
Publisher: 日本生物工学会
Enhancement of introduced gene expression in mammalian cells by heat shock and a prostaglandin derivative.

Matsuda Taichi, Tanigawa Takahiro, Hikida Masaki, Takai Toshiyuki, Ohmori Hitoshi

5　195-195　1993
Publisher: 日本生物工学会
Stimulation of introduced gene expression in mammalian cells by 5-azacytidine and L-azetidine-2-carboxylic acid.

Matsuda Taichi, Tanigawa Takahiro, Hikida Masaki, Takai Toshiyuki, Yasuda Tatsuji, Takebe Yutaka, Ohmori Hitoshi

4　188-188　1992
Publisher: 日本生物工学会
Establishment of a target cell line for the assay of cytotoxic T cell activity.

Ohmori Hitoshi, Takai Toshiyuki, Honma Yoichi, Tanigawa Takahiro

3　159-159　1991
Publisher: 日本醗酵工学会
ニワトリ成長過程における肝アセチルCoAカルボキシラーゼmRNAの変動

田辺忠, 高井俊行, 横山知永子

脂質生化学研究　31　159-162　1989/07
Publisher: 日本脂質生化学会
ISSN： 0285-1520

Show all ︎Show first 5

Presentations 140

Immunoreceptors Regulating Autoantibody Production in Aging. International-presentation

TAKAI Toshiyuki

Tohoku Forum for Creativity Thematic Program 2017 Aging Science: from Molecules to Society　2017/05/11
免疫制御と疾患におけるIgGとFcレセプター. Invited

高井俊行

第3回FcR研究フォーラム2017　2017/03/01
Regulatory receptor LILRB4 characterizes pathogenic plasma cells in SLE. International-presentation

TAKAI Toshiyuki

11th International Symposium of The Institute Network “Frontiers in Biomedical Sciences”　2017/01/27
免疫制御と疾患におけるIgGとFcレセプター. Invited

高井俊行

Fc Summit　2016/11/26
川崎病患者に対する免疫グロブリン大量療法前後における抑制性受容体LILRB発現の変化について.

久間木悟, 乾匡範, 飛内章子, 三浦舞子, 目時嵩也, 渡邊庸平, 大沼良一, 野口理恵, 貴田岡節子, 高井俊行

日本川崎病学会　2016/09/30
TREM2/DAP12を介するミクログリア活性化は神経障害性疼痛を増悪させる.

小西博之, 小林正明, 高井俊行, 木山博資

第59回日本神経化学会大　2016/09/08
全身性エリテマトーデスにおけるBリンパ球系細胞の抑制性受容体. Invited

高井俊行

第65回日本アレルギー学会学術大会　2016/06/18
Regulatory receptors characterizing peripheral B-lineage cells in SLE. International-presentation Invited

TAKAI Toshiyuki

Antibody and Fc Receptor Biology: Bench to Bedside–A Special Symposium to Honor Jeffrey V. Ravetch on his 65th Birthdayシンポジウム　2016/05/09
B-cell regulatory receptors in SLE. Invited

高井俊行

第44回日本免疫学会学術集会共催テクニカルセミナー　2015/11/18
自己抗体の産生源を探る. Invited

高井俊行

第11回東北大学REDEEMシンポジウム　2015/09/12
Roles of Inhibitory Immunoreceptors in Autoimmunity. International-presentation Invited

高井俊行

International Mini-symposium for immune regulation　2015/04/06
疾患制御におけるIgGとFcレセプター. Invited

高井俊行

免疫グロブリンセミナー2015　2015/03/04
Putative B1 cells and plasmablasts are distinguishable in their inhibitory receptor expression and immunoglobulin secretion profiles.

Wong Yi Li, INUI Masanori, TAKAI Toshiyuki

第43回日本免疫学会学術集会　2014/12/12
The endoplasmic reticulum-resident membrane protein Nogo-B modulates Toll-like receptor responses to nucleic acids in macrophages.

KIMURA Toshihfumi, INUI Masanori, TAKAI Toshiyuki

第43回日本免疫学会学術集会　2014/12/11
ヒトFcRⅡの免疫制御における役割. Invited

高井俊行

第1回FcRフォーラム研究会2014　2014/10/22
血小板を介する新たな炎症制御機構の同定.

乾匡範, 田澤樹乃, 岸義朗, 高井俊行

第87回日本生化学会大会　2014/10/17
Nogo-B(Reticulon 4B) regulates unreacellular TLR pathway through interaction with GRAMD4.

木村俊文, 乾匡範, 高井俊行

第87回日本生化学大会　2014/10/17
Fc受容体による自己免疫の制御. Invited

高井俊行

第79回インターフェロン・サイトカイン学会学術集会　2014/06/19
Modulation of Toll-like receptor signaling by Nogo in macrophages.

木村俊文, 乾匡範, 高井俊行

第42回日本免疫学会学術集会　2013/12/13
Identification of a novel regulatory pathway of inflammation via platelets.

田澤樹乃, 乾匡範, 髙井俊行

第42回日本免疫学会学術集会　2013/12/13
抑制性Fcレセプターによる自己抗体の産生制御. Invited

高井俊行

Advanced Seminar Series on Microbiology and Immunology　2013/11/12
抑制性FcレセプターFcγRIIBによる自己抗体の産生制御. Invited

高井俊行

金沢医科大学大学院医学系セミナー　2013/06/14
Negative Regulation of Autoantibody Production by a B Cell Inhibitory. International-presentation

TAKAI Toshiyuki

2013/05/10
Negative Regulation of Autoantibody Production by a B Cell Inhibitory Receptor, FcγRIIB. International-presentation Invited

高井俊行

Centennial of Hashimoto Disease Symposium, International Symposium II: Autoimmune Diseases–Etiology and Therapeutics　2012/12/03
Autoimmune disease in B6.Slam129 mice.

Kanari Y, Sugahara-Tobinai A, Takai T

CREST Workshop on Inflammation and Autoimmunity　2012/11/15
Regulatory effects of IgG on B cell functions. Invited

高井俊行

RCAI Workshop　2012/03/23
Updata understanding of the mechanism of action of IVIG. International-presentation

高井俊行

10th International Kawasaki Disease Symposium　2012/02/08
Regulation of TLR9 and autoimmunity by PirB, a multiligand inhibitory receptor. Invited

高井俊行

Second CSI/JSI/KAI Joint Symposium on Immunology “Regulation of Immune Responses in Health and Diseases”　2011/12/06
Differential but competitive binding of Nogo and MHC class I to PIR-B regulates LPS-activated mast cells.

Shinozaki N, Inui M, Endo S, Sakamoto Y, Kitaguchi K, Kuroki K, Maenaka K, Takai T

2011 The annual meeting of the Japanese society for immunology　2011/11/29
Transcriptional activation of the PIR-B gene in B cells by PU.1 and Runx3.

Kitaguchi K, Arita K, Endo S, Kaifu T, Nakamura A, Takai T

2011 The annual meeting of the Japanese society for immunology　2011/11/28
A suppressive effect of IVIg on B1 cell activation and production of natural antibodies.

Hirano K, Tanaka J, Sakamoto Y, Looi CY, Nakano A, Itoh Y, Takai T

The annual meeting of the Japanese society for immunology　2011/11/27
Fcγ receptor targeting–How ITIM receptors regulate. International-presentation Invited

高井俊行

Bio-Rheumatology International Congress (BRIC) Tokyo / The 8th GARN Meeting　2011/11/15
NogoおよびMHCクラスIによるPIR-Bへの競合的結合によるマスト細胞の制御について

篠﨑夏子, 乾匡範, 遠藤章太, 坂本譲, 北口公司, 高井俊行

第61回日本アレルギー学会秋季学術大会　2011/11/11
NogoおよびMHC class IによるPIR-Bを介した新たなマスト細胞の制御機構

乾匡範, 篠﨑夏子, 遠藤章太, 高井俊行

第61回日本アレルギー学会秋季学術大会　2011/11/11
抗体療法とFcレセプター Invited

高井俊行

第31回日本川崎病学会・学術集会ランチョンセミナー２　2011/10/01
Fc受容体と免疫疾患について Invited

高井俊行

第16回シェーグレン症候群セミナー　2011/06/04
Targeting Fc receptors. Invited

高井俊行

第32回日本炎症・再生医学会　2011/06/02
Regulation of TLR9 activation and autoantibody production in B-1 cells by PIR-B, an MHC class I receptor. International-presentation Invited

高井俊行

8th German–Japanese Symposium.　2010/09/26
Regulation of autoimmunity by PIR-B. International-presentation Invited

高井俊行

Asian Aging Core for Longevity 2010　2010/08/22
自己免疫疾患におけるIVIG療法の作用機序の最新知見 Invited

高井俊行

献血ベニロン-I発売30周年記念講演会　2010/07/10
Regulation of cytotoxic T lymphocyte activity by CD8 and PIR-B. International-presentation

Endo S, Sakamoto Y, Kobayashi E, Nakamura A, Takai T

The 5th International Symposium of Institute Network　2010/06/24
制性受容体による免疫制御機構の解析

高井俊行

日本薬学会第130年会　2010/03/28
A novel regulatory system for TLR9 and autoimmunity mediated by PIR-B in B-1 cells. International-presentation Invited

高井俊行

Tohoku University Gloval COE “Network Medicine” The 1st International Symposium　2009/12/07
免疫抑制性レセプターPIR-Bによるアレルギー制御 Invited

高井俊行

第59回日本アレルギー学会秋季学術大会　2009/10/29
Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells. International-presentation Invited

高井俊行

2009 4th Medical Biotech Forum.　2009/08/08
Fcレセプターによる免疫制御について Invited

高井俊行

第43回大和免疫アレルギー研究会　2009/07/14
Immunogenicity and Antibodies as Immunodiagnostics. International-presentation Invited

Takai T, Kubo T, Uchida Y, Watanabe Y, Abe M, Nakamura A

BIT’s 1st Annual International Congress of Antibody-2009 Beijing　2009/05/09
Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive rheumatoid factor production and autoimmunity. International-presentation Invited

高井俊行

BIT’s Life Sciences’ 2nd Annual Protein and Peptide Conference (PepCon 2009)　2009/04/03
Activation of osteoclastogenesis by ITAM-bearing immunoreceptors Invited

高井俊行

日本分子生物学会BMB2008　2008/12/11
Fc受容体と自己免疫． Invited

高井俊行

52回日本リウマチ学会総会・学術集会シンポジウム　2008/04/20
Regulation of autoimmunity by PIR-B, an inhibitory receptor for class I MHC. International-presentation Invited

高井俊行

The Joint Symposium of the 3rd International Symposium of Institutes Network and Hot spring Harbor International Symposium” Cell-fate Decision: Function and Dysfunction in Host Defense -Tumor, Infection and Immunity- Venue　2008/02/02
ペア型制御レセプターPIRのクラスI MHC認識を介した免疫調節機構 Invited

高井俊行

生化学会，分子生物学会合同年会ワークショップ　2007/12/11
「自己免疫疾患におけるIVIGの作用機序とFcレセプター」

高井俊行

第27回日本川崎病研究会ランチョンセミナー　2007/10/11
Immune regulation by PIR-B, a novel receptor for MHC class I molecules International-presentation

Toshiyuki Takai

Centre of Excellence Joint Symposium　2007/09/05
A murine inhibitory integrin gp49B negatively regulates dendritic cell function in vitro and in vivo

KASAI Satoshi, INUI Masanori, NAKAMURA Akira, TAKAI Toshiyuki

第36回日本免疫学会総会・学術集会　2006/12/26
Constitutive binding of PIR-B to MHC class I regulates mast cell activation and anaphylaxis

NAKAMURA Akira, SAKAMOTO Yuzuru, TAKAI Toshiyuki

第36回日本免疫学会総会・学術集会　2006/12/11
Regulation of human osteoclast development by LILRB4 in vitro

MORI Yu, INUI Masanori, TSUJI Sukenao, NAKAMURA Akira, TAKAI Toshiyuki

第36回日本免疫学会総会・学術集会　2006/12/11
Regulation of in vitro osteoclast development by paired Ig-like receptor (PIR)-B

TSUJI Sukenao, INUI Masanori, MORI Yu, NAKAMURA Akira, TAKAI Toshiyuki

第36回日本免疫学会総会・学術集会　2006/12/11
Paired immunoglobulin-like receptor (PIR)-B on antigen-presenting cells recognize MHC class I expressed on T cells at the immunological synapus

SAKAMOTO Yuzuru, NAKAMURA Akira, TAKAI Toshiyuki

第36回日本免疫学会総会・学術集会　2006/11/11
Hydronephrosis associated with anti-urothelial and anti-nuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice

Taku Okazaki, Yumi Otaka, Jian Wang, Toshiyuki Takai, Jeffrey V. Ravetch, d Tasuku

国際分子生物学会京都　2006/10/24
破骨細胞の分化をコントロールする免疫系のレセプター」

高井俊行, 招待講演, 東北大加齢

東北大学大学院歯学研究科インターフェインターフェイス口腔健康科学第１５回学術フォーラム　2006/07/19
Paired Immunoglobulin-like Receptor (PIR)-Bによるリガンド認識機構

小林栄治, 小林圭輔, 中村晃, 高井俊行

第1回COE相互交流、若手研究者の会　2006/07/14
“Role of paired immunoglobulin-like receptor (PIR)-B in allergic responses”

Takai T, speaker, IDAC, Tohoku Universi

RCAI-JSI International Symposium on Immunology　2006/06/16
“Role of paired immunoglobulin-like receptor (PIR)-B in allergic responses”

高井俊行

RCAI-JSI International Symposium on Immunology　2006/06/16
Regulation of human osteoblast development by LILRB4 in vitro. 1st International-presentation

Mori Y, Inui M, Tsuji S, Nakamura A, Takai T (IDAC, Tohoku Universi

International Conference on Osteoimmunology　2006/05/28
Cis binding of PIR-B to MHC class I on mast cells suppress allergic responses International-presentation

Nakamura A, Masuda A, Maeda T, Takai T, ite, Speaker, IDAC, Tohoku Universi

Immunology 2006　2006/05/12
Enhanced mucosal IgA responses in PIR-B deficient mice International-presentation

Kobayashi R, Alabama at Birmingham, USA, Kubagawa H, Takai T, Sekine S, McGhee J.R, Fujihashi K

Immunology 2006　2006/05/12
Fcg receptors participate in the development of autoimmune diabetes in NOD mice International-presentation

Inoue Y, Nakamura A, Takai T (IDAC, Tohoku Universi

Immunology 2006　2006/05/12
「Paired immunoglobulin-like receptor (PIR)-B欠損樹状細胞によるMHCクラスI拘束性抗原提示の増強」

遠藤章太, 中村晃, 高井俊行

東北免疫研究会　2006/03/17
Fcレセプター

高井俊行, 指定講演, 東北大加齢

第35回日本免疫学会総会・学術集会　2005/12/13
Fcレセプター

高井俊行, 指定講演, 東北大加齢

第35回日本免疫学会総会・学術集会レビュートーク　2005/12/13
Involvement of Fcγ receptors in the autoimmune type I diabetes of NOD mice

Inoue Y, Nakamura A, Takai T (IDAC, Tohoku Universi

第35 回日本免疫学会総会・学術集会　2005/12/13
Enhanced MHC class I-restricted antigen presentation by Paired immunoglobulin-like receptor (PIR)-B deficient dendritic cell

Endo S, Nakamura A, Takai T (IDAC, Tohoku Universi

第35 回日本免疫学会総会・学術集会　2005/12/13
LANIER Lewis L.、荒瀬尚:NK細胞の活性化 CD200レセプターを介した新たな標的細胞認識機構

石川哲, 阪大, 微研, 免疫化学, 千葉大, 院医, 加齢呼吸器病態制御学, 白鳥行大, 荒瀬規子, 高井俊行

第35回日本免疫学会総会・学術集会　2005/12/13
Plexin-A1 utilizes the Trem-2/DAP12 receptor complex as a co-receptor in the immune system

Takegahara N, Kumanogoh A, Takamatsu H, Takai T, Kikutani H, Dept.Molecular, Immunology, BIKEN, Osaka Un

第35回日本免疫学会総会・学術集会　2005/12/13
Fcレセプター International-presentation

高井俊行

2005年日本免疫学会総会・学術集会レビュートーク　2005/12/13
新しい自己認識レセプターPIRによる免疫制御と疾患

高井俊行, 指定講演, 東北大加齢

2005年日本分子生物学会シンポジウム　2005/12/07
免疫系における分子認識とその制御

高井俊行, 指定講演, 東北大加齢

2005年日本分子生物学会シンポジウム「免疫系における分子認識とその制御」　2005/12/07
新しい自己認識レセプターPIRによる免疫制御と疾患

高井俊行

2005年日本分子生物学会シンポジウム「免疫系における分子認識とその制御」　2005/12/07
イムノグロブリンとその受容体をめぐる最近の話題最近の話題

高井俊行, 招待講演, 東北大加齢

第１回神経治療を考える会　2005/11/21
イムノグロブリンとその受容体をめぐる最近の話題

高井俊行, 招待講演, 東北大加齢

第１回神経治療を考える会　2005/11/21
「免疫制御レセプターFcRとPIRをめぐる最近の話題」

高井俊行

献血ベニロンI発売２５周年記念学術講演会　2005/11/11
免疫制御レセプターFcRとPIRをめぐる

高井俊行, 招待講演, 東北大加齢

愛媛県医師会主催　2005/11/11
免疫制御レセプターFcRとPIRをめぐる最近の話題

高井俊行

愛媛県医師会主催免疫制御レセプターFcRとPIRをめぐる最近の話題　2005/11/11
PIRによる新しい自己認識システム

高井俊行

神戸大学大学院医学研究科セミナー　2005/09/13
加齢と免疫〜調節性レセプターの観点から〜

高井俊行

第１回加齢皮膚医学研究会　2005/08/20
Immunoreceptors, calcium, and bone remodeling International-presentation

Takai T, ite, Speaker, IDAC, Tohoku Universi

Gordon Conference on Bones and Teeth　2005/07/13
PIRによるMHCクラスI分子認識とその意義

高井俊行, 招待講演, 東北大加齢

第５回日本蛋白質科学会年会ワークショップ「免疫シグナル伝達におけるタンパク質の分子認識」　2005/07/01
破骨細胞分化におけるPaired Immunoglobulin-like receptor (PIR)-Bの役割の検討

乾匡範, 辻佑直, 森優, 高井俊行

「シグナル伝達病の治療戦略創生拠点」COE第2回若手研究交流会　2005/07/01
IgGとアレルギー

高井俊行, 教育講演, 東北大加齢

第17回日本アレルギー学会春季臨床大会　2005/06/01
Fcレセプターによる免疫制御とその応用

高井俊行

東京小児感染免疫懇話会　2005/05/24
Exacerbated GVHD in mice devoid of PIR-B, an inhibitory receptor for MHC class I molecules

Takai T, ite, Speaker, IDAC, Tohoku University

. The Sixth Nagoya International Blood and Marrow Transplantation Symposium　2005/05/22
PIRによる新しい自己認識システム

高井俊行, 招待講演, 東北大加齢

科学技術振興機構2005年第１回基礎研究報告会　2005/04/15
Establishment of Immortalized Natural Killer Cell Lines with Natural Killing and Cytokine Production from Temperature-sensitive SV40T Transgenic Mice International-presentation

Kaifu T, Iizuka S, Itou K, Obinata M, Takai T (IDAC, Tohoku Universi

Experimental Biology 2005　2005/04/02
Fcγレセプターによる免疫制御と疾患

高井俊行, 招待講演, 東北大加齢

第23回日本耳鼻咽喉科免疫アレルギー学会　2005/03/03
PIRによる新しい自己認識システム

高井俊行

群馬大学生体調節研究所ゼミ　2005/02/21
FcレセプターとPIRによる免疫制御と疾患

高井俊行

三風会　2005/01/28
GVHDにおけるPaired Immunoglobulin-like Receptorの役割

高井俊行, シンポジウム招待講演

第27回日本造血細胞移植学会スポンサードシンポジウム２「GVHD：基礎研究から臨床応用への時代　2004/12/16
A novel MHC class I recognition system by Paired immunoglobulin-like receptor

中村晃, 小林栄治, 高井俊行

第27回日本分子生物学会年会　2004/12/08
: A novel MHC class I recognition system by paired immunoglobulin- like receptor

小林栄治, 中村晃, 高井俊行

第27回日本分子生物学会年会　2004/12/08
Exacerbated Graft-versus-Host Disease in PIR-B-Deficient Mice

Takai T, Nakamura A, Kobayashi E, Invi

日米医学協力計画40周年記念事業シンポジウム　2004/12/08
Exacerbated Graft-versus-Host Disease in PIR-B-Deficinet Mice

Toshiyuki Takai, Akira Nakamura, Eiji Kobayashi

40th Anniversary United States？Japan Cooperative Medical Science Program　2004/12/07
Paired immunoglobulin-like receptor (PIR)による移植片対宿主病 (GVHD)の制御

中村晃, 小林栄治, 高井俊行

第34回日本免疫学会総会・学術集会　2004/12/02
Sema6Dはplexin-A1を介して免疫細胞を活性化する

竹ヶ原宣子, 熊ノ郷淳, 山本みどり, 高松漂太, 識名崇, 丸川聡子, 石田勲, 高井俊行, 菊谷仁

第34回日本免疫学会総会・学術集会　2004/12/02
アダプター分子DAP12およびFcR?を介するITAMシグナルは破骨細胞分化に必須である

乾匡範, 古賀貴子, 井上和也, 谷口維紹, 高柳広, 高井俊行

第34 回日本免疫学会総会・学術集会　2004/12/02
ITAM-dependent costimulatory signals are essential for the maintenance of bone homeostasis

Inoue K, Inui M, Koga T, Taniguchi T, Takayanagi H, Takai T (IDAC, Tohoku Universi

第77回日本生化学学会大会　2004/10/14
ITAM-dependent costimulatory signals are essential for the maintenance of bone homeostasis

Inoue K, Inui M, Koga T, Taniguchi T, Takayanagi H, Takai T (IDAC, Tohoku Universi

第77回日本生化学学会大会　2004/10/14
ITAMを介した共刺激シグナルはRANKLによる破骨細胞分化に必須である

古賀貴子, 乾匡範, 末松綾子, 谷口維紹, 高井俊行, 高柳広

日本骨代謝学会　2004/08/04
ITAMを介した共刺激シグナルはRANKLによる破骨細胞分化に必須である

古賀貴子, 乾匡範, 末松綾子, 谷口維紹, 高井俊行, 高柳広

日本骨代謝学会　2004/08/04
Augmented anaphylactic responses due to hypersensitive mast cells in PIR-B-deficient Mice International-presentation

Nakamura A, Masuda A, Maeda T, Takai T (IDAC, Tohoku Universi

International congress of immunology　2004/07/26
Defective ligation of paired Ig-like receptor (PIR)-B to MHC Class I molecules leads to exacerbated graft-versus-host disease (GVHD) International-presentation

Nakamura A, Kobayashi E, Takai T. (IDAC, Tohoku Universi

International congress of immunology　2004/07/26
Establishment and characterization of novel mast cell lines derived from temperature-sensitive mutant of SV40 large T antigen transgenic mice International-presentation

Kanehira M, Yumi Y, Ito K, Kaifu T, Nakamura A, Obinata M, Takai T (IDAC, Tohoku Universi

International congress of immunology　2004/07/26
Antigen targeting to Fc?RIIB and Fc?RI/III on bone marrow-derived dendritic cells efficiently elicits humoral response and cytotoxic T lymphocytes in vivo International-presentation

Endo S, Akiyama K, Yada A, Ebihara S, Matsumura K, Maeda T, Nakamura A, Aiba S, Nukiwa T, Takai T(IDAC, Tohoku Universi

International congress of immunology　2004/07/26
Immortalized dendritic cell line with efficient cross-presentation ability established from transgenic mice harboring temperature-sensitive SV40 large T-antigen gene International-presentation

Kaifu T, Ebihara S, Endo S, Itoh Y, Akiyama K, Nakamura A, Obinata M, Takai T. (IDAC, Tohoku Universi

International congress of immunology　2004/07/26
Exacerbated graft-versus-host diseases in Pirb-/-mice International-presentation

Kobayashi E, Nakamura A, Takai T (IDAC, Tohoku Universi

International congress of immunology　2004/07/26
: Exacerbated graft-versus-host disease in Pirb-/-mice International-presentation

Eiji Kobayashi, Akira Nakamura, Toshiyuki Takai

12th International Congress of Immunology and 4th Annual Conference of FOCIS　2004/07/18
ペア型イムノグロブリン様受容体PIR-BによるGVHDの抑制

高井俊行

第7回造血器腫瘍シンポジウム　2004/07/10
Defective ligation of PIR-B to MHC class I molecules leads to accelerated graft-versus-host disease (GVHD) International-presentation

Nakamura A, Kobayashi E, Takai T. (IDAC, Tohoku Universi

Experimental biology 2004　2004/04/26
Augmented anaphylactic responses in PIR-B-deficient mice International-presentation

Masuda A, Maeda T, Nakamura A, Takai T. (IDAC, Tohoku Universi

Experimental biology 2004　2004/04/26
Targeting apoptotic tumor cells to Fc? receptors provides efficient and versatile vaccination against tumors by dendritic cells International-presentation

Akiyama K, Ebihara S, Yada A, Matsumura K, Aiba S, Nukiwa T, Takai T (IDAC, Tohoku Universi

International Symposium on Predictive Oncology and Intervention　2004/02/26
DAP12遺伝子欠損マウスの骨形成異常と視床中心性のミエリン形成低下，劣性遺伝子Nasu-Hakora との関連について

乾匡範, 高井俊行

.第25回日本分子生物学会年会　2003/12/13
サンドホフ病における抗ガングリオシド抗体による中枢神経系への影響

山口章, 勝山佳代子, 山中正二, 高井俊行, 青木一郎

第26回日本分子生物学会年会　2003/12/13
GM2 GangliosidesとFcR : FcR 欠損によるサンドホフ病モデルでの神経症状の改善

山口章, 勝山佳代子, 山中正二, 高井俊行, 青木一郎

第33回日本免疫学会総会・学術集会　2003/12/10
Paired Immunoglobulin-like Receptor(PIR)-Bによるマスト細胞の恒常的抑制

前田努, 高井俊行

第33回日本免疫学会総会　2003/12/09
Paired Immunogobuli-like Receptor (PIR)-Bによるマスト細胞の恒常的抑制

前田努, 増田愛, 中村晃, 高井俊行

第33回日本免疫学会総会・学術集会　2003/12/09
温度感受性SV40 Large T抗原トランスジェニックマウスからの株化マスト細胞の樹立ならびに機能解析

兼平雅彦, 伊藤梢, 伊藤由美, 中村晃, 高井俊行

第33回日本免疫学会総会　2003/12/09
Synergistic regulation of autoimmune disease by PD-1 and Fc?RIIB

Otaka Y, e, t, Med. Chem, Kyoto University, Okazaki T, Wang J, Takai T, Honjo T

第33回日本免疫学会総会・学術集会　2003/12/09
温度感受性SV40Large Tトランスジェニックマウス由来の新規樹状細胞クローンによる強い抗腫瘍活性

遠藤章太, 海老原伸, 前田努, 秋山健一, 伊藤梢, 伊藤由美, 中村晃, 高井俊行

第33回日本免疫学会総会　2003/12/08
抑制性免疫グロブリン受容体FcγRIIBと自己免疫疾患

高井俊行

第35回日本小児感染症学会総会　2003/11/07
DAP12 deficiency results in osteopetrosis and thalamic hypomyelinosis with synaptic degeneration International-presentation

Inui M, Nakahara J, Kaifu T, Mishima K, Momiyama T, Kaji M, Sugahara A, Koito H, Ujike-Asai A, Nakamura A, Kanazawa K, Tan-Takeuchi K, Iwasaki K, Yokoyama W.M, Kudo A, Fujiwara M, Asou H, Takai T (IDAC, Tohoku Universi

HUPO 2nd annual and IUBMB XIX Joint World Congress　2003/10/26
PIR-B欠損マウスにおけるI型アレルギーの亢進．アレルギー

高井俊行

PIR-B欠損マウスにおけるI型アレルギーの亢進．アレルギー学会総会シンポジウム8：関連トピックス　2003/10/24
T helper 2-prone immune responses and enhanced severity of anaphylaxis in Paired Immunoglobulin-like Receptor(PIR)-B-deficient mice

高井俊行

第76回日本生化学大会　2003/10/18
Antigen targeting to Fc? receptors on bone marrow-derived dendritic cells efficiently elicits humoral response and cytotoxic T lymphocytes In Vivo

Endo S, Akiyama K, Yada A, Ebihara S, Matsumura K, Maeda T, Nakamura A, Aiba S, Nukiwa T, Takai T (IDAC, Tohoku Univer

International Workshop on Langerhans Cells　2003/09/26
FcRおよびPIR-Bによるアレルギーの制御Inhibition of allergic responses by FcR and PIR-B

高井俊行

国際痒みシンポジウム大阪　2003/09/06
痴呆を必発する那須ハコラ病の脂質代謝異常の病態生理の解析

高井俊行

財団法人小野医学研究財団第14回研究成果発表会　2003/06/07
Increased susceptibility to LPS-induced endotoxin shock in Secretory leukoprotease inhibitor (SLPI)-deficient mice International-presentation

Nakamura A, Mori Y, Hagiwara K, Suzuki T, Kikuchi T, Ebina M, Takai T, Nukiwa T

Association of Immunologists IMMUNOLOGY 2003　2003/05/26
Yajima K, Nakamura A, Sugahara A, Takai T International-presentation

Yajima K, Nakamura A, Sugahara A, Takai T

Association of Immunologists IMMUNOLOGY 2003　2003/05/26
PIR-B欠損マウスにおけるI型アレルギーの亢進

高井俊行

第15回日本アレルギー学会春季臨床大会　2003/05/12
Increased Susceptibility to LPS-Induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-Deficient Mice International-presentation

中村晃, 高井俊行

米国免疫学会　2003/05/10
FcγRIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease International-presentation

高井俊行

米国免疫学会　2003/05/09

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Industrial Property Rights 19

IMMUNE CHECKPOINT INHIBITOR

Toshiyuki TAKAI, Masanori INUI, Shota ENDO, Mei-Tzu SU

Property Type: Patent
炎症性疾患のマーカー

高井俊行, 石井智徳, 藤井博司, 乾匡範

Property Type: Patent
リウマチ関節炎高発症モデルマウス

中村晃, 貫和敏博, 高井俊行

特許3570674

Property Type: Patent
大理石骨病モデル非ヒト動物

高井俊行, 高柳広, 乾匡範, 古賀貴子

特許5230893

Property Type: Patent
移植片対宿主病モデル動物

高井俊行, 中村晃

特許5242882

Property Type: Patent
脳組織変性の診断方法

高井俊行, 西條芳文, 菅原章子

特許4550356

Property Type: Patent
ギランバレー症候群及び／又はフィッシャー症候群発症モデル非ヒト動物

高井俊行, 中村晃, 矢島佳央里

Property Type: Patent
骨髄由来の不死化樹状細胞株

高井俊行, 海老原伸, 帯刀益夫, 伊藤由美, 伊藤梢

特許4219789

Property Type: Patent
死化ナチュラルキラー細胞株

高井俊行, 飯塚悟, 帯刀益夫, 伊藤由美, 伊藤梢

特許4033390

Property Type: Patent
免疫応答の誘導方法

秋山健一, 高井俊行, 貫和敏博

Property Type: Patent
Th2型過剰免疫応答モデル非ヒト動物

高井俊行, 氏家あづさ

特許3926603

Property Type: Patent
全身性エリテマトーデスモデル非ヒト動物

高井俊行, 中村晃, 矢島佳央里

特許4653915

Property Type: Patent
オリゴデンドロサイト発達障害モデル非ヒト動物

高井俊行, 阿相皓晃, 藤原道弘

Property Type: Patent
III型アレルギー炎症モデル動物

湯浅貴恵, 小野栄夫, 渡邊武, 高井俊行

特許3453348

Property Type: Patent
Fc受容体を介する寄生虫感染症治療薬のスクリーニング方法

名和行文, 小野栄夫, 高井俊行

Property Type: Patent
Goodpasture症候群モデルマウス

中村晃, 貫和敏博, 高井俊行

特許3410679

Property Type: Patent
Mice mutant for Fc receptors and method of treating autoimmune disease.

effrey V. Ravetch, Toshiyuki Takai, Dianna Sylvestre, Raphael Clynes

特許U.S. Patent 5,877,396

Property Type: Patent
脱リン酸化酵素を阻害する新規ペプチド

高井俊行, 山下由美, 小野栄夫

Property Type: Patent
アナフィラキシー抑制物質のスクリーニング方法

濱田宗雄, 岡本全泰, 中田勝彦, 高井俊行

Property Type: Patent

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Research Projects 31

Mechanism of LILRB4-mediated immune checkpoint

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2019/04/01 - 2022/03/31

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Regulatory mechanism of the immune checkpoint LILRB4 expressed mainly on myeloid-lineage cells such as macrophages and dendritic cells has not been clarified yet. We successfully identified its physiological ligand as fibronectin (FN), more specifically its N-terminal 30 kDa domain (FN30). We also found that upon recognition of FN30 by LILRB4, this regulatory receptor could suppress FN-binding integrin signal as well as focal adhesion-related signal associated with cell adhesion. Our findings identify for the first time a unique regulator of cell-adhesion-related intracellular signal.
Modulating immunological memory of antibody-producing cells

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tohoku University

2017/06/30 - 2020/03/31

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We established an experimental system composed of culturing murine bone marrow-derived mesenchymal stem cells (MSC) and plasma cells (PC) in vitro and monitoring antibody production levels after the 7-day culture. We found that the antibody production by PC was influenced by IL-6 and other soluble factors secreted by MSC and unidentified direct interaction between MSC and PC. We also suggested that the direct interaction involves binding between an immunoregulatory receptor LILRB4 (B4) on PC and a novel B4 ligand, B4L1, expressed on MSC.
Identification of molecular characteristics of pathogenic autoantibody-producing cells

TAKAI Toshiyuki, Inui Masanori, Itou Ari, Endo Shota, Su Mei-Tzu

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2016/04/01 - 2019/03/31

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In this study, first we have found that expression of leukocyte immunoglobulin-like receptor (LILR)B4, an inhibitory member of the human LILR family, is augmented in autoantibody-producing plasmablasts/plasma cells (PCs) of systemic lupus erythematosus (SLE) patients. However, the mechanism behind the upregulation of LILRB4 upon pathogenic antibody-secreting cells is yet to be known. To clarify the mechanism, next we have examined if glycoprotein 49B (gp49B), the murine counterpart of human LILRB4, is also elevated in autoantibody-producing cells in several SLE mouse models. We have found that gp49B is indeed expressed on PC of SLE-prone models but not of healthy C57BL/6 mice, and the level was positively correlated to the autoantibody IgG titer in serum. Gp49B genetic deletion, however, did not abolish the serum autoantibodies or fully ameliorate the lethal glomerulonephritis, indicating that gp49B is not the sole regulator of lupus but a pathogenic element in the disease.
The role of immunosuppressive receptor LILRB in the pathogenesis of Kawasaki disease, and its application to the therapy.

Kumaki Satoru

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Department of Clinical Research, National Hospital Organization Sendai Medical Center

2014/04/01 - 2017/03/31

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Kawasaki disease (KD) is an acute vasculitis of unknown pathogenesis which occurs most frequently in early childhood, and intravenous immunoglobulin (IVIG) is effective. To obtain a mechanistic insight into the humoral immune response in KD patients, B cell subpopulations and the expression pattern of immunosuppressive receptor LILRB was analyzed. As a result, proportion of memory B cells increased in acute phase of the KD patients when compared with normal controls. Furthermore, the proportion of plasmablasts was significantly elevated in the acute phase of KD, which returned to the basal level after IVIG. From these results, it was suggested that adaptive immunity is involved in the pathogenesis of KD. In addition, we demonstrate that the expression of LILRB4 was enhanced in the acute phase of KD, and the expression was controlled by IVIG. These results suggest that plasmablasts with increased LILRB4 expression play an important role in the pathogenesis of KD.
Platelets convert peripheral blood circulating monocytes to regulatory cells via immunoglobulin G and activating-type Fcg receptors.

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2014/04/01 - 2016/03/31

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Augmented production of an immunoregulatory cytokine IL-10 with a concomitant reduction of proinflammatory cytokines in macrophages in vitro is attained by doubly stimulating the cells with a TLR ligand and IgG immune complexes, a response known as that of regulatory macrophages. However, it has not been explored sufficiently how such a regulatory response occurs in more physiologic settings. We showed that IgG-opsonized platelets convert human peripheral blood circulating monocytes to IL-10-producing regulatory monocytes in vitro and in vivo. This novel way of enhancing IL-10 was mediated by activating-type Fc receptor FcγRIIA. A therapeutic preparation of human polyclonal IgG (or IVIG) was found to react to platelets via the Fab portion, thereby converting circulating monocytes to regulatory cells. These findings indicate that the IgG-bound platelet-induced conversion provides a novel mechanism for homeostatic generation of regulatory monocytes.
The role and networks of immune and nonimmune cells in the small intestine in the early stage of gastrointestinal parasite infection.

MORIMOTO Motoko, TAKAI TOSHIYUKI

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Miyagi University

2013/04/01 - 2016/03/31

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The coordinated actions of lymphocytes, innate immune cells, epithelium, and smooth muscles can play an important role in host intestinal immune function and homeostasis. We investigated type2 immune responses in early stage against nematode parasite in the murine intestine. The results suggested that innate immune cells initiate production of type2 cytokines, communicate with other immune cells including T cells and mediate adaptive pathogen-specific immune responses to eliminate pathogens. INFgamma; might regulate the termination of innate immune responses in the early stage. While, Th2 play mainly in memory responses against re-infection of nematode parasite.
Novel immune regulation by PirB-related multiple ligands

TAKAI Toshiyuki, INUI Masanori, ENDO Shota

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2012/04/01 - 2015/03/31

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We have attempted to elucidate a whole spectrum of PirB (or human LILRB)-mediated immune regulation through its binding to the multiple ligands such as Nogo and MHC class I molecules, and to develop novel therapeutic strategies against immune disorders such as allergy and autoimmune diseases. We have found that Nogo is preferentially localized to endoplasmic reticulum and regulates TLR9-mediated immune activation via interacting with GRAMD4 but not PirB. Also, we have characterized a human novel B-lineage cell subset, CD43+ B cells, as an intermittent pre-plasmablastic population but not human B1-like cells, being positioned between memory B cells and plasmablasts in terms of its surface LILRB expression, antibody and cytokine secretion, and transcriptional factor expression profiles.
Elucidation of Regulatory Mechanism of B1 Cells by Human IgG Natural Antibodies

TAKAI TOSHIYUKI

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2012/04/01 - 2014/03/31

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We defined human peripheral blood CD20+CD27+CD43+CD70- B cells as "putative (puB1) B1 cells", and characterized them in terms of expression profiles for B cell inhibitory receptors including several isoforms of ILT/LILR and Ig production. We found a grossly similar profiles of the inhibitory receptors on puB1 cells and memory B cells, but distinctive receptor expression and Ig secretion profiles between the puB1 subset and CD43high plasmablasts.
免疫抑制受容体PIR-Bによる自己応答性の制御

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 特定領域研究

Institution: 東北大学

2010 - 2011

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【研究内容】自己の分子認識機構を解明するため,本年度はB1細胞,B2細胞におけるPIR-Bとそのリガンドによる抗体産生制御の機構の解析に注力した。【研究結果】新たなPIR-Bのリガンドであることが示唆されたNogoについて,Nogo欠損マウスの表現型の解析を行った。またヒトB細胞集団の中で,マウスB1細胞に相当すると思われるサブセットが同定されたため(Griffin DO et al., J. Exp. Med. 2011)これに倣い末梢血B細胞集団中のB1細胞の分画,表面LILRBアイソフォーム発現の解析を行った。結果として,Nogo欠損はB細胞分化の過程と末梢での維持に影響を与えることが分かった。また「ヒト末梢血からCD20,CD27,CD43発現を指標としてごくマイナーな分画であるB1細胞の集団を分取できることが分かった。興味深いことにこの集団は前記マーカーの発現のみならずB2細胞と異なる抑制系レセプターLILRB発現プロファイルを示すことが示唆され,さらにこれが末梢血単球のLILRB発現プロファイルとも異なる傾向にあった。【成果の意義】B細胞の制御は,非自己に効果的に反応する一方で自己への有害な反応を回避するために極めて重要である。このシステムが崩壊すると自己抗体が過剰に生産されて自己免疫疾患を惹起する。そのためB細胞は多様な制御機能を持った分子群により調節されている。自己反応性を有する血中抗体のソースであるB細胞のうち,マイナーなB1細胞集団の分画ができるようになり,B1細胞とB2細胞の抗体産生に関する抑制機構の相違を示唆する知見が得られた。PIR-B,ヒトLILRB,そのリガンドNogo等の抑制性受容体システムの調節により免疫学的な自己の確立が維持される可能性が示唆された。本研究により免疫疾患を予防,治療することも可能になる将来展開の基盤が構築された。
Prediction of immune disorders by evaluation of serum IgG reactivity to random peptide library

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2010 - 2011

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Based on an assumption that reactivities of natural antibodies in sera will be changed before and after onset of immune disorders such as autoimmune diseases, we first analyzed the effect of human polyclonal IgG preparations on immune cell functions such as that of B cells. We found that F(ab')_2 fragment of IgG can bind to various cell surfaces and swiftly internalized into the cytosol. Interestingly, the polyclonal IgG was able to suppress cytokine production from B cells stimulated with CpG.
Molecular Basis for the Immune Regulatory Receptor System

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2008 - 2010

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Paired immunoglobulin-like receptor (PIR)-B, an immunoreceptor tyrosine-based inhibitory motif-harboring receptor for MHC class I molecules, could participate in the regulation of B-1 cells, because PIR-B expression is several times higher in B-1 cells than in B-2 cells or conventional B cells. Recent unexpected findings pointed to a novel inhibitory role of PIR-B in neurite regeneration through binding to three axonal outgrowth inhibitors of myelin including Nogo. Thus, it becomes interesting to determine whether the actions of the inhibitory myelin proteins and MHCI could coexist or be mutually exclusive as to the PIR-B-mediated immune and neural cell inhibition. We studied this subject and obtained data supporting the coexistence of Nogo- and MHCI-mediated inhibition. We now propose a novel mechanism by which PIR-B-mediated regulation is achieved dually via MHCI and Nogo in cells of the immune system.
免疫抑制受容体PIRーBによる自己応答性の制御

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 特定領域研究

Institution: 東北大学

2008 - 2009

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いくつかのB細胞表面の抑制性レセプターの欠損マウスに共通して見ちれる現象として,自然免疫を担うB1細胞集団の増加がある。B1細胞の自己増殖性を維持するためにはB細胞受容体から入力されるシグナルが必要であり,これを抑制性受容体が阻害するため,と大くくりに理解されているが,その実体はよく分かっていない。他の抑制性受容体欠損の場合と同様にPIR-B(ヒトLILRB1/B2に相当)欠損においても腹腔B1細胞が加齢とともに増加する現象が見られていたが(Ujike A.et al.A.Nat.Immunol.2002),我々はB1細胞からのIgMタイプのリウマチ因子(RF;抗IgG Fc自己抗体)の産生が特に亢進していること,さらに今回,世界に先駆けて,Fas^<Ipr>変異との合併によりこの産生が顕著に亢進してIgGタイプのRFが増加し,糸球体腎炎を発症して死亡率が上昇することを観察した。この制御機構においてはTLR9の活性亢進が関係し,PIR-B欠損によってとりわけBtkのリン酸化が亢進してこれがTLR9下流のNF-κBのリン酸化亢進につながっていることが解明された(Kubo et al.J.Exp.Med.2009)。現在ではさらにB1細胞,およびB2細胞上でのPIR-Bの制御様式,B細胞レセプターやTLRシグナルの制御,細胞膜上での動態,抗体産生制御,新規リガンドの探索と作用解明を進めている。
免疫抑制レセプターgp49B/LILRB4の新機能に関する研究

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 萌芽研究

Institution: 東北大学

2007 - 2008

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gp49Bおよびそのヒト相同分子LILRB4は, 樹状細胞(DC)の末梢性免疫寛容の維持に大きく貢献している可能性が代表者らの最近の研究により強く示唆される免疫抑制レセプターである. 近年, 免疫細胞の機能制御に関わる多様なレセプターが同定され, 様々な免疫反応の制御に重要な役割を演じていることが明らかになってきている. Ig-like receptor分子群がその中で主要なファミリーを形成しており, これにはFcreceptor, leukocyte Ig-like receptor(LILR), paired Ig-like receptor(PIR)などが含まれ, DC上では活性化型と抑制性のレセプターが共に発現し, DCの機能をそれぞれ正または負に制御する. これらのレセプターによる寛容誘導性DC(tolerogenic DC)の分化制御機構, 寛容維持の機構について分子レベルで活発な展開がスタートしようとしているのが世界的潮流である. 本年度の研究ではこの寛容誘導性DCの分子メカニズムにおいて, 世界で初めてgp49Bの関与を証明し, その機構を, gp49Bに結合するT細胞上のインテグリンv3を含めたリガンドとの相互作用によることを明確に示した. これにより, DC, 更には骨髄系細胞上のgp49BおよびLILRB4などがT細胞や他の細胞上のリガンドとの相互作用を経て免疫制御を行っていることを利用した免疫制御方法の開発, および免疫病の治療方法の開発に道を拓くことになった.
Pre-Translational Approaches to the Conquest of Immune Disorders by Targeting Fcγ Receptors

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2005 - 2007

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Fc receptors play pivotal roles in immune regulation, and their dysregulation leads to immune-related diseases including allergic inflammationand aud autoimmunity. We have obtained in this project the following accomplishments: 1) Establishment of the importance of inhibitory Fcγ receeptor, FcγRIIB, in immune regulation and autoimmune dieseases, such as autoimmune glomerulonephritis. 2) Establishment of animal models for immune disorders by the use of Feγ receptor gene-targeted mice. 3) Establishment of immune cells with the immortalized growth and immune functions by the use of SV40LT-transgenic mice. Among these, in particular, we have identified the pivotal roles of activating-type Fcγ receptors, but not inhibitory FcγRIB, in the development of autoimmune diabetes of NOD mice. Type 1 diabetes mellitus (T1D) in humans is an organ-specific autoimmune disease in which pancreatic islet β cell are ruptured by autoreactive T cells. NOD mice, the most commonly used animal model of T1D, show early infiltration of leukocytes in the islets (insulitis), resulting in islet destruction and diabetes later. NOD mice produce various islet β cell-specific autoantibodies, although it remains a subject of debate regarding whether these autoantibodies contribute to the development of T1D or not. To investigate the possible role of FcγRs in NOD mice, we have generated several FcγR-less NOD lines, namely FcR common γ chain (FcRγ)-deficient ((NOD.γ^<-/->), FcγRIII-deficient (NOD.III^<-/->), FcγRIIB-deficient (NOD.IIB^<-/->), and both FcRγ and Fcγ and FcγRIIB-deficient NOD (NOD.null) mice. We have shown significant protection from diabetes in NOD.γ^<-/->, NOD.III^<-/->, and NOD.null but not in NOD.IIB^<-/-> mice even with grossly comparable production of autoantibodies among them. Insulitis in NOD.γ^<-/-> mice was also alleviated. Adoptive transfer of bone marrow-derived dendritic cells or NK cells from NOD mice rendered NOD.γ^<-/-> animals more susceptible to diabetes, suggesting a possible scenario in which activating FcγRIII on NK cells trigger antibody-dependent effector functions and inflammation. These findings highlight the critical roles of activating FcγRs in the development of T1D, and indicate that FcγRs are novel targets for therapies for T1D.
イムノグロブリン様受容体分子郡による破骨細胞分化制御に関する研究

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 萌芽研究

Institution: 東北大学

2005 - 2006

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慢性関節リウマチにおける骨軟骨破壊のメカニズムの一つとして,破骨細胞の分化と異常活性化が挙げられる.しかしながら破骨細胞の分化プロセス,活性化プロセスにどのような分子機構がはたらいているのかについては十分に理解されていない.これまで破骨細胞の分化には骨芽細胞などから提供されるRANKL (receptor activator of NF-κB ligand)が必要十分と考えられていたが,我々はRANKL以外に多数のIgLR群が活性化する必要があることを突き止めた.つまりIgLRの活性化に利用されている膜アダプターであるFcRγとDAP12が同時に欠損することで破骨細胞の試験官内での分化は完全に阻害され,このマウスは重度の大理石骨病となる.破骨細胞のこの経路による活性化にはPIR-A,OSCAR,TREM-2,SIRPβ1などの既知の活性化型IgLR群および未知の活性化型IgLR群が関与していることが示された.この成果により,慢性関節リウマチ患者の破骨細胞のはたらきの制御は,IgLRを介する活性化経路を人為的に修飾することで達成できる可能性が指摘される.さらに抑制系レセプターの破骨細胞分化に及ぼす影響について研究を進め,PIR-B,ヒトのLILRBのアイソフォームのいくつかのものが破骨細胞上に発現して実際に破骨細胞分化を制御していることを示すデータが得られつつある.これらの成果は破骨細胞分化制御において,免疫系細胞と同様の抑制プロセスの存在を示唆するものであり,その創薬への応用を含めて今後の展開が期待できるレベルに達した.
IMMUNE REGULATION BY IMMUNOGLOBULIN-LIKE RECEPTORS

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2002 - 2004

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PIRs expressed on B and myeloid cells form a unique 'self' recognition. Activating PIR-A and inhibitory PIR-B were shown to bind various murine MHC class I (H-2) molecules. In vitro H-2 tetramer stimulation of PIRs induced intracellular phosphotyrosine signaling. PIR-B-deficient mice transferred with allogeneic splenocytes showed exacerbated graft-versus-host disease, which was due to the augmented activation of the recipient's dendritic cells (DCs) with the concomitant up-regulation of PIR-A and increased IFN-production. PIR-A-induced DC activation also led to increased proliferation of donor cytotoxic T cells. Thus, PIR-A and PIR-B are counter-acting receptors that play key roles for successful tissue transplantation, and may regulate irrelevant reaction to autologous tissues in a constitutive fashion under physiological circumstances. To analyze the etiology of mild osteopetrosis in DAP12 (DNAX protein 12)-deficient mice, we examined the bone morphology in FcRγ-deficient (FcRγ--) mice and DAP12/FcRγ double deficient (DKO) mice. Histological examination revealed that FcRγ--mice did not show any remarkable osteopetrosis. However, we found that DKO mice exhibited much more severe osteopetrosis than DAP12--mice, suggesting that either DAP12 or FcRγ is required for normal bone remodeling. In osteoclast precursor cells, FcRγ and DAP12 associate with multiple IgLRs including OSCAR and PIR-A ; and TREM-2 and SIRPβ1, respectively, and activate Ca^2 signal through PLCγ. Thus, ITAM-dependent costimulatory signals activated by multiple IgLRs are indispensable for the maintenance of bone homeostasis, indicating that RANK and M-CSF receptor are not sufficient to activate signals required for osteoclastogenesis.
Fc受容体による中枢神経系の制御機構

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 萌芽研究

Institution: 東北大学

2002 - 2003

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1970年代初頭に初めて症例が報告されたNasu-Hakola病は,多発性の病的骨折,および性格変化などの統合失調症に似た精神神経症状ののち若年性痴呆を必発して死に至る,予後不良の劣性遺伝病である.フィンランドのグループの地道な家系調査とゲノムスクリーニングの結果,2000年に至ってNasu-Hakola病の原因が,免疫系において見い出されていた活性化シグナル伝達を担う膜アダプター分子、DNAX activating protein(DAP)12をコードする遺伝子の欠損であることが同定された.我々はNasu-Hakola病の発症機序を解明する目的でDAP12欠損マウスを作製し,骨および中枢神経系におけるDAP12の役割を検討したところ,このマウスは破骨細胞の発達障害ならびにオリゴデンドロサイトの視床領域での発達障害を示すことを見いだした.Nasu-Hakola病の原因として,従来から脂質代謝の異常,あるいは血管壁の変化によって惹起された大脳白質の慢性循環障害とする説など,確定されていなかったが,DAP12欠損マウスでは脂質代謝異常,ならびに大脳血管の内皮細胞に異常は見いだせなかった.とりわけヒトで若年性の痴呆に至る過程は全く不明であり,DAP12欠損マウスでは2年齢の老化マウスでさえ明白な行動異常は観察されないし、神経細胞の顕著な減少も見られない.DAP12が如何なるレセプターと会合し,その生理的リガンドは何なのか.さらにそのリガンドの脳内分布はどのようになっているのか,などの基本的な知見を蓄積することがヒトのNasu-Hakola病とDAP12欠損マウスとの間に存在する分子レベルでの相違の同定につがなり,これがいずれヒトの精神分裂病や若年性痴呆のひとつのメカニズムの解明につながることを目指したい.本年度は特に骨疾患についての更なる解析を行い,DAP12とともにFcRγも骨形成に関与していることを突き止め,これらアダプター分子群がイムノグロブリン様受容体分子群と会合し,RANKLからのシグナルとともに破骨細胞形成に不可欠であることを解明した.
Fc受容体を介したIgE,IgGによるマスト細胞機能の調節

高井俊行, 中村晃

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 特定領域研究

Institution: 東北大学

2000 - 2003

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Immunoglobulin(Ig)-like receptor(IgLR)という範疇に属する新規なレセプター分子群が続々と単離され,その機能が注目され始めてまだ5年ほどしか経過していないが,これらが免疫調節に重要な役割を担う証拠が次々と挙がっている.マウスのPaired IgLR(PIR)は活性化シグナルを伝達するPIR-Aと,逆に抑制性シグナルを伝達するPIR-Bのペアからなる代表的なIgLRであるが,PIR-Bが欠損するとB細胞,樹状細胞のシグナル伝達が撹乱され,その免疫応答はTh2型に著しく偏ることを我々は本研究課題において示してきた.本年度は,正常な免疫応答に不可欠であるこのレセプター・ペアが何を認識し,どのようなシグナルを細胞内に導入しているのか,さらに免疫疾患にどのように関連しているのかを明らかにすることでマスト細胞機能,およびアレルギーや自己免疫などの発症に関する新規な機構を解明することを目的とした.その縞果,PIR-B,PIR-AともにMHC class I分子を認識し,PTR-Bの欠損によって移植片対宿主反応が亢進してホストのGVHDが増悪することが分かった,さらにマスト細胞はこの識別機構を喪失した結果,刺激感受性が増大し,アレルギーを発症しやすくなる素地を形成することが分かった.したがってPIRはTCRやKIRとともに自己MHC class Iを認識する第3のシステムを構築し,自己反応性および外界からの無用な刺激応答性を回避していることが示唆された.
Development of Autoimmune Disease Models Based on FcyRIIB-Deficient Mice

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2000 - 2001

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The receptors for Fc protion of immunoglobulins, Fc receptors (FcRs), combine innate and adaptive immunity and are critical elements to activate or down-modulate the immune responses. Activity of various cells in the immune system is intimately regulated by the balanced signaling through FcRs. Development of many autoimmune diseases in humans may now be interpreted by the impairement in the FcR regulatory system. To address the question whether the type IIB Fc receptor for IgG (FcγRIIB)-deficient mice (RIIB-/-) are susceptible to induction of various autoimmune diseases, we tested to induce type II collagen-induced arthritis (CIA), a model for rheumatoid arthritis in humans. We found that RIIB-/- on a non-permissive H-2b background become susceptible to CIA induction. Moreover, we could induce Goodpasture' s syndrome (GPS) in RIIB-/- by immunization with type IV collagen. Quite similar to human GPS, RIIB-/- develop massive pulmonary hemorrhage and glomerulonephritis. These results highlight the role of FcγRIIB in maintaining tolerance and suggest that it may play a critical role in the pathogenesis of rheumatoid arthritis and GPS in humans.
Analysis of Physiological Roles of Novel Immunoglobulin-Like Receptors, PIR

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

1999 - 2001

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Paired immunoglobulin-like receptor (PIR)-B inhibits receptor-mediated activation signaling in vitro, while neither the physiological role nor ligand for PIR has been elucidated. PIR-B-/- mice had an increased number of peritoneal B-1 cells with age that, along with splenic B-2 cells, were hypersensitive to B cell receptor ligation. T helper (TH)2-prone humoral responses were augmented in the mutant mice upon immunization with T-dependent antigens in terms of both interleukin-4-rich/interferon-γ-poor cytokine profile and enhanced IgG1 and IgE production. Impaired maturation of dendritic cells possibly due to perturbed intracellular signaling was responsible for the skewing. Thus, PIR-B is critical for B cell suppression, DC maturation, and for balancing TH1/TH2 immune responses.
Molecular mechanism of response of living body to environmental stress

TAMURA Shinri, KOBAYASHI Takayasu, HIRAGA Akira, TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

1998 - 2001

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Protein phosphatase 2C (PP2C) is implicated in the negative regulation of tress-activated protein kinase (SAPK) cascades in yeast and mammalian cells. In this study, we determined the role of PP2Cβ-1, a major isoform of mammalian PP2C, in the TAK1 signaling pathway, a SAPK cascade that is activated by interleukin-1 (IL-1), transforming growth factor-β or stress. Ectopic expression of PP2Cβ-1 inhibited the TAK1-mediated mitogen-activated protein kinase kinase 4 (MKK4)-c-Jun N-terminal kinase (JNK) and MKK6-p38 signaling pathways. In vitro, PP2Cβ-1 dephosphorylated and inactivated TAK1. Co-immunoprecipitation experiments indicated that PP2Cβ-1 associates with the central region of TAK1. A phosphatase-negative mutant of PP2Cβ-1, PP2Cβ-1(R/G), acted as a dominant negative mutant, inhibiting dephosphorylation of TAK1 by wild-type PP2Cβ-1 in vitro. In addition, ectopic expression of PP2Cβ-1(R/G) enhanced IL-1-induced activation of an AP-1 reporter gene. Collectively, these results indicate that PP2Cβ negatively regulates the TAK1 signaling pathway by direct dephosphorylation of TAK1.
樹状細胞Fcγ受容体へのがん抗原ターゲティングによるがん免疫賦活方法の開発

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 特定領域研究(C)

Institution: 東北大学

2000 - 2000

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樹状細胞(DC)に発現されているFcγレセプター(FcγR)に特定の癌抗原あるいは癌細胞をIgG免疫複合体として試験管内で結合させ,処理させることでDCの抗原提示能を飛躍的に亢進させる.これを担癌マウスに移入することで癌抗原特異的免疫応答を誘導する方法を開発することを目的とした.DCによる免疫賦活では,非特異的に抗原を取り込ませる方法,および糖鎖レセプターなどを介して取り込み効率を上昇させる方法が検討されている.レセプターを介する方法は少量の抗原で済むため効率良く行える利点があるが,糖鎖など特定のレセプターに認識される構造を持っていないものについては利用できない難点がある.今回の方法はどのような蛋白質であっても,それに対する特異的IgG抗体との複合体にすることでDC上のFcγRに結合させることができ,CD4+およびCD8+T細胞の活性化を誘導する抗原提示をおこなうことが可能となる.本法が発展することで癌の新規免疫療法の開発が行えるようになることが期待される.本年度はまずDCのFcγRへの抗原ターゲティングによりCD4+T細胞への抗原提示能力が約100倍亢進する結果が得られた.さらにCTLに対する活性化も得られることが分かり,特異的FcγRターゲティングにより癌免疫の賦活が可能であることが示された.
NK細胞の分化におけるFcR,KAR,gp49の役割に関する研究

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 特定領域研究(A)

Institution: 東北大学

2000 - 2000

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ナチュラルキラー(NK)細胞の分化と機能獲得に関してはその多くが未だ謎に包まれている.NK細胞はヒト末梢血中に5%程度存在し,前感作なしに異種細胞や自己の異常細胞を破壊する,いわゆる自然免疫の一翼を担う細胞である.本研究の目的は,KARの活性化シグナル伝達を司るKARAP分子の欠損マウス,機能未知なgp49分子欠損マウス,そしてFcRγ鎖欠損マウスにおけるNK細胞の分化状態および標的細胞破壊機能を調査し,KAR分子群,FcR分子群,gp49分子群とNK細胞の分化との関係を解明する.本年度はgp49B欠損マウス,KARAP欠損マウスの作製を完了し,解析を行ったところ,gp49が欠損していてもNK細胞は正常に分化しており,標的細胞の障害もコントロールと同等の能力を有していることを見いだした.またKARAP欠損マウスにおいてはNK細胞は正常に分化し,一般的標的細胞に対しては正常な障害能力を有する一方,中枢神経系に異常が見られることが発見された.
炎症のバイオサイエンスの新しい展開

宮坂昌之, 高井俊行, 松島綱治, 義江修, 長澤丘司, 木全弘治

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 大阪大学

1999 - 1999

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最近、炎症反応を媒介する接着分子、ケモカイン、Fcレセプターなどの分子群が次々に同定され、炎症反応の分子生物学は飛躍的な進歩を遂げつつある。しかし、各分野を越えての研究交流は比較的少なかった。このため本研究では、これらの研究を行っている第一線の研究者10名を集め、お互いの持つ新知見を交換するとともに、新しい戦略の構築にむけて統合的な活動を行った。特にわが国で発見された新規ケモカイン、Fcレセプター、接着分子間のクロストーク現象の解析、これらの分子を標的とした抗炎症剤免疫抑制剤の開発に向けて活動を行った。そして、その成果を公開することを目的として、平成11年12月21日(火)に大阪大学銀杏会館において文部省科学研究費基盤C1公開シンポジウム「炎症のバイオサイエンスの新しい展開」を行った。このシンポジウムでは全班員による公開発表を行うとともに、関連研究者、聴衆に対する啓蒙活動を行った。
ナチュラルキラー細胞の分化におけるFcR,KAR,gp49の役割に関する研究

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 特定領域研究(A)

Institution: 東北大学

1999 - 1999

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ナチュラルキラー(NK)細胞の分化と機能獲得に関してはその多くが未だ謎に包まれている.NK細胞はヒト末梢血中に5%程度存在し,前感作なしに異種細胞や自己の異常細胞を破壊する,いわゆる自然免疫の一翼を担う細胞である.本研究の目的は,KARの活性化シグナル伝達を司るKARAP分子の欠損マウス,機能未知なgp49分子欠損マウス,そしてFcRg鎖欠損マウスにおけるNK細胞の分化状態および標的細胞破壊機能を調査し,KAR分子群,FcR分子群,gp49分子群とNK細胞の分化との関係を解明する.本年度はgp49B欠損マウス,KARAP欠損マウスの作製を完了し,解析を開始した.また各種FcR欠損マウスにおける胎児胸腺中のNK細胞とT細胞の分化について,胎児胸腺培養系を構築し,FcRに対する抗体を添加した際のNK細胞とT細胞の分化の変化を追跡できるようになった.FcRがNK細胞の分化に影響を及ぼしていることを示唆するデータが得られた.gp49B欠損マウスについてもこの培養系を応用し,興味深い知見を得た.
ANALYSIS OF IGA NETWORK BY GENE TARGETING

TAKAI Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: OKAYAMA UNIVERSITY

1996 - 1997

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We hae found a novel murine cell-surface glycoprotein, designated as q91, expressed mainly in myeloid cells such as macrophages and mast cells. The molecule has six immunoglobulin-line extracellular domains, a transmembrane segment, and a cytoplasmic tail containing four immunoreceptor tyrosine-based inhibition motif (ITIM) or ITIM-like sequences, resembling the structural features of human killer-cell inhibitory receptors (KIR). p91 comprises a polymorphic gene family, harboring one potent inhibitory-type p91 and at least two other p91 genes. Tyrosine-phosphorylated, but not nonphosphorylated, synthetic peptides matching each of the third ITIM and the fourth ITIM-like sequences found in the cytoplasmic portion of p91A,the sole inhibitory-type p91, associated with the tyrosine phosphatases SHP-1 and SHP-2. In addition, the phosphotyrosyl peptide matching the third ITIM sequence also bound the inositol 5-phosphatase SHIP. Thses results support the notion that p91A may function as an inhibitory cell-surface molecule against cell activation. The p91 genes were shown to be clustered in the proximal region of mouse chromosome 7, a syntenic position of human chromosome 19 where the genes for the KIR family are found. A human cDNA clone cross-hybridizing to a murine p91 probe was isolated from a human spleen cDNA library, and was found to be coding for a molecule quits similar to members of the immunoglobulin-like transcript (or ILT) family. The gene was found to locate on human chromosome 19q13.3-13.4. These results will establish the existence of a novel set of potent regulatory receptors in mouse and man, similar but different from the KIR family.
Fcレセプター欠損マウスを用いたアレルギーの分子機構の解明とその修復法の開発

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 重点領域研究

Institution: 岡山大学

1996 - 1996

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イムノグロブリン・スーパーファミリーに属する分子などの細胞内領域にimmunoreceptor tyrosine-based activation motif (ITAM)と呼ばれるアミノ酸配列が存在する場合,このモチーフはチロシンキナーゼの基質となることでその後の細胞活性化シグナリングに重要な役割を演じる.最近,ITAMのコア配列であるYXXL/Iに類する配列を有し,かつ細胞内シグナリングに抑制的にはたらくモチーフであるITIMおよびその抑制メカニズムが注目されている.ITIMを持つ分子としてこれまでNKレセプター,CD22,Fcレセプター(FcR),CTLA-4などが知られているが,これまでの知見ではITIMは,ITAMと同様にチロシンキナーゼによりリン酸化されたのち細胞内の脱リン酸化酵素SHP-1やSHIPとアソシエ-トすることで抑制機能を発揮するらしい.これまで本研究者はITAMを持つFcRγ鎖のノックアウトおよびITIMを持つFcγRIIBのノックアウトマウスを作成し,これらの免疫機能を解析した.FcRはこれまで,液性免疫と細胞性免疫の調節因子としての役割や,炎症・アレルギーとの関係を中心にその機能の解析が進められてきたが,FcRγ鎖ノックアウトマウスではマクロファージの貧食機能が消失するなど,種々のエフェクター機能が消失し,炎症の開始機構においてFcεRIやFcγRIIIが中心的役割を担っていることが示された.逆にFcγRIIBノックアウトマウスにおいては抗体応答や貧食機能に亢進が見られ,更にIgGを介するアナフィラキシ-や接触過敏症反応,コラーゲン関節炎などが野生型マウスに比べ強く現れることを観察した.即ち,免疫システムの抑制機構としてFcγRIIBを介する経路が存在することが示された.よって生体は,IgG免疫複合体とFcγRによる,免疫系を活性化あるいは抑制する巧妙な調節システムを備えていると理解できる.
Fc受容体遺伝子ノックアウトマウスを用いた免疫制御機構の解析

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 重点領域研究

Institution: 岡山大学

1995 - 1995

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Fcレセプター(FcR)は,IgGやIgEのFc部分と結合することで免疫系の細胞内に情報伝達を行う分子群である.以前からFcRは.抗体や補体を中心とする体液性免疫と,エフェクター細胞を中心とする細胞性免疫との間の橋渡し役として免疫系を調節しているのではないかと考えられてきたが,FcRノックアウトマウスの作成により,個々のFcRの生理的機能を詳細に解き明かすことができるようになった。まず,(1)FcRγサブユニット欠損マウスの作成により,マクロファージの貧食機能が消失するなど,FcRγ鎖が複数のFcRの共通のサブユニットでることを証明し,アレルギーの開始機能においてFcRが中心的役割を担っていることを示した。また(2)FcγRII欠損マウス作成により,抗体応答などに顕著な亢進が見られる事を見い出し,免疫応答にはFcγRIIを介する負のフィードバック機構が存在することを明らかにした.即ち,これまでアレルギーといえばIgEこそメインであり,炎症エフェクター細胞がIgEを介してどのように活性化されるかという機序の解明が中心課題であると考えられてきたが,実は生体にはIgGとそのレセプターであるFcγRIIによる,免疫系を巧妙に抑制するシステムが存在しているということが明らかになったわけである.
遺伝子ターゲティングによるFcγ受容体欠損マウスの作成およびその解析に関する研究

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 奨励研究(A)

Institution: 岡山大学

1994 - 1994

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[目的]Fcγレセプター(FcγR)は、免疫担当細胞表面上に存在し、IgGのFc部分と結合することでエフェクター機能の発現の引金を引く重要な分子である。マウスII型FcγRは、ほとんど全ての血球系細胞に発現しており、B細胞では抗原レセプターを介する情報伝達に対して抑制的に作用することが示唆されているが、詳細は明かでない。今回我々は、FcγRIIの生理的機能を個体レベルで明らかにするために、胚性幹(ES)細胞での遺伝子ターゲティングによってFcγRII欠損マウスを作成した。[方法及び結果]マウスFcγRII遺伝子を単離し、Neo^R遺伝子及びヘルペス・TK遺伝子を組み込んだターゲティング・ベクターを構築した。これをES細胞J1及びE14にトランスフェクトし、G418とFIAU両耐性となったクローンの中から、サザンブロット法により相同組換え体を同定した。これらをマウス初期胚にマイクロインジェクションしてキメラ個体を得、これらと野生型マウスとの交配により、FcγRIIヘテロ欠損個体を得た。現在、ホモ欠損個体の作成を行っており、今後これらのマウスにおける各種免疫機能の解析を行う予定である。
遺伝子ノックアウト法による免疫グロブリンGFc受容体の機能解析

高井俊行

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 奨励研究(A)

Institution: 岡山大学

1993 - 1993

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免疫グロブリンFc受容体(FcR)は免疫担当細胞の膜表面上に存在し、抗原抗体複合体の結合によって貧食活性、細胞傷害活性、エフェクター細胞からの炎症メディエーターの放出などの引金を引く重要な分子である。しかしその分子的実体が遺伝子クローニングによって明らかになったのは比較的最近であり、IgGのFcR(FcgammaR)はマウスでは3種類存在し、それぞれ発現されている免疫担当細胞に特異性が見られることなどが解明された。申請者は、近年特にその有用性と結果の明快さが注目されている遺伝子ノックアウト法に着目し、これまで生体の免疫系においてその機能がほとんど分かっていないII型FcgammaRの機能を遺伝子ノックアウト法を用いて明らかにするために以下の研究を行った。まず、129系マウスのゲノムライブラリーからII型FcgammaRのcDNAをプローブとして遺伝子を単離し、制限酵素マップを作成した。相同組換え効率を上昇させるためにポリ(A)トラップタイプのベクターおよび通常のpPNTを骨格としたターゲティングベクターの構築に取り組み、相同領域が約7.5kbと約8.5kbのベクターを組み立てた。これらを129系マウス由来の胚幹(ES)細胞であるJ1にトランスフェクトし、G418およびFIAUを用いる2重選択により両耐性のES細胞クローンを単離した。これらのゲノムDNAのサザンプロットによる解析の結果、数個のクローンにおいてII型FcgammaR遺伝子座にターゲティングが起こっていることを確認した。現在C57BL/6マウス由来の胚にこれらのクローンをマイクロインジェクションし、キメラマウスの作成に取り組んでいる。
Molecular biological study on the regulation of fatty acid biosynthesis

TANABE Tadashi, TAKAI Toshiyuki, YOKOYAMA Chieko, IMADA Masaru

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for General Scientific Research (C)

Institution: National Cardiovascular Center Research Institute

1988 - 1989

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Fatty acids are essential substance for organisms as membrane components, energy sources etc. Accumulation of fatty acids, however, causes various cardiovascular diseases and obesity. In the present study we have investigated the regulatory mechanism of fatty acid biosynthesis to overcome these diseases. According to the previous study by our and other groups, biosynthesis of fatty acid is regulated by modulating the activity of acetyl-CoA carboxylase (ACC). Following results have been obtained by the present study. 1. With use of our cDNA clones of chicken liver ACC as probes and specific antibodies, expression of ACC was studied. ACC mRNA and the enzyme protein was found in liver, brain, testis, kidney, lung and heart. The changes of the hepatic and heart contents of ACC mRNA and the enzyme protein in growing chicks were measured. In the post-hatching period, the bepatic mRNA markedly increased at least 70- fold when compared to that before hatching. This increase was not observed in chicks receiving no diet These changes were closely paralleled with the rise of the hepatic content of ACC protein in chicks up to 10 days old. Contents of ACC mRNA and the enzyme protein in heart were not changed during development. 2. Primary structure of various biotin-dependent carboxylase including chicken and rat liver ACC was compared and a genealogical tree was constructed. The results indicated the animal ACC, a multifunctional polypeptide has been formed by gene fusion of monofunctional polypeptide chains found in Escherichia coli ACC during molecular evolution. The result is completely agreed with the previous enzymological observations of biotin-dependent enzymes. 3. Cloning of ACC gene has been attempted by screening human genomic libraries with chicken ACC cDNA as a probe and the obtained colones covered approximately 40 kb of the gene. The 13.4 kb-region of the gene was characterized. The 404 residues of the protein-coding region determined was distributed into 4 exons. The deduced primary structure of human ACC coincided with that of chicken and rat enzymes in 95 and 98 %, respectively. Cloning and characterization of the remaining portion of the gene are now in progress.

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Social Activities 5

[日本国内] 加齢研における中学校理科教諭研修会

2004/09/16 - Present

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中学校理科教諭研修会
[日本国内] 夏休み大学探検

2004/09 - Present

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市内中学生有志への研究室公開（仙台市教育委員会主催）
[日本国内] 中学生職場見学

2001/07 - Present

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研究室公開
[日本国内] 「私たちはこんな病気と闘っています３」

2007/10/09 -

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大理石骨病などの難病とそれに向き合う患者，家族たちの紹介番組「私たちはこんな病気と闘っています３」（TBS系列 2007年10月9日火曜夜9時〜2時間放送）においてDAP12/FcRgamma二重欠損マウスの骨組織像（Koga et al. Nature 2004）が利用された．
[日本国内] 「科学技術振興機構戦略的創造研究推進事業CREST研究から」

2006/02/24 -

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[日本国内] 科学技術振興機構戦略的創造研究推進事業CREST研究から

科学新聞

2006/02/24

Type: Newspaper, magazine
[日本国内] 骨髄移植成功へのカギ免疫抑制たんぱく質発見東北大

読売新聞

2004/05/17

Type: Newspaper, magazine
[日本国内] 骨髄移植の拒絶反応和らげるたんぱく質東北大発見

日経新聞

2004/05/17

Type: Newspaper, magazine
[日本国内] 骨髄移植などの不適合反応抑制遺伝子を発見東北大

毎日新聞

2004/05/17

Type: Newspaper, magazine
[日本国内] 骨髄移植合併症抑制の受容体を発見東北大グループ

産経新聞

2004/05/17

Type: Newspaper, magazine
[日本国内] 骨髄移植成否握るタンパク質発見

河北新報

2004/05/17

Type: Newspaper, magazine
[日本国内] 骨髄移植の成否を握るタンパク質の発見について

NHK

2004/05/17

Type: TV or radio program

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Other 2

ミエリン発達障害を非侵襲的に検出する新規な精神・神経障害診断法の開発

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ミエリン発達障害を非侵襲的に検出する新規な精神・神経障害診断法の開発
Fc受容体による中枢神経系グリアの発達制御機構の解明

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Fc受容体による中枢神経系グリアの発達制御機構の解明