Details of the Researcher

PHOTO

Mutsumi Furukawa
Section
Graduate School of Agricultural Science
Job title
Assistant Professor
Degree

  • 博士（農学）（東北大学）

  • 修士（農学）（東北大学）

e-Rad No.
80914267

Research History 1

  • 2019/04 - 2021/03
    日本学術振興会特別研究員（DC2）

Education 3

  • Tohoku University　Graduate School of Agricultural Science　Division of Life Science

    2018/04 - 2021/03

  • Tohoku University　Graduate School of Agricultural Science　Division of Life Science

    2015/04 - 2018/03

  • Tohoku University　Faculty of Agriculture　Department of Applied Bio-Sciences

    2011/04 - 2015/03

Awards 4

  1. 令和２年度 東北大学 農学研究科長賞

    2021/03　東北大学

  2. 令和２年度 東北大学 総長賞

    2021/03　東北大学

  3. 平成29年度 東北大学 農学研究科長賞

    2018/03　東北大学

  4. 第66回東北畜産学会 優秀発表賞

Papers 20

  1. Breast milk stabilizes bacterial communities in the large intestine even after weaning

    Kaori Ito, Jahidul Islam, Kota Sakurai, Saeka Koyama, Ayumi Matsuo, Kunihiro Okano, Ryota Hirakawa, Mutsumi Furukawa, Tomonori Nochi

    Biochemical and Biophysical Research Communications　151585-151585　2025/03

    Publisher: Elsevier BV

    DOI： 10.1016/j.bbrc.2025.151585 　

    ISSN： 0006-291X

  2. Freeze-dried fecal microorganisms as an effective biomaterial for the treatment of calves suffering from diarrhea

    Jahidul Islam, Natsuki Ohtani, Yu Shimizu, Masae Tanimizu, Yoshiaki Goto, Masumi Sato, Eiji Makino, Toru Shimada, Chise Ueda, Ayumi Matsuo, Yoshihisa Suyama, Yoshifumi Sakai, Niel A. Karrow, Hiroshi Yoneyama, Ryota Hirakawa, Mutsumi Furukawa, Hidekazu Tanaka, Tomonori Nochi

    Scientific Reports　14　(1)　2024/11/14

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-024-79267-5 　

    eISSN： 2045-2322

  3. Formation of the junctions between lymph follicles in the Peyer's patches even before postweaning activation

    Anri Teshigahara, Yuri Banba, Hiromi Yoshida, Mitsuji Kaji, Zhou Zhou, Nao Koyama, Yoshifumi Sakai, Niel A. Karrow, Kouetsu Ogasawara, Ryota Hirakawa, Jahidul Islam, Mutsumi Furukawa, Tomonori Nochi

    Scientific Reports　14　(1)　2024/07/09

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-024-65984-4 　

    eISSN： 2045-2322

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    Abstract Peyer’s patches (PPs), which contain an abundance of B and T cells, play a key role in inducing pivotal immune responses in the intestinal tract. PPs are defined as aggregated lymph follicles, which consist of multiple lymph follicles (LFs) that may interact with each other in a synergistic manner. LFs are thought to be spherical in shape; however, the characteristics of their structure are not fully understood. To elucidate changes in the structure of PPs as individuals grow, we generated serial 2D sections from entire PPs harvested from mice at 2, 4, and 10 weeks of age and performed a 3D analysis using a software, Amira. Although the number of LFs in PPs was not changed throughout the experiment, the volume and surface area of LFs increased significantly, indicating that LFs in PPs develop continuously by recruiting immune cells, even after weaning. In response to the dramatic changes in the intestinal environment after weaning, the development of germinal centers (GCs) in LFs was observed at 4 and 10 weeks (but not 2 weeks) of age. In addition, GCs gradually began to form away from the center of LFs and close to the muscle layer where export lymphatic vessels develop. Importantly, each LF was joined to the adjacent LF; this feature was observed even in preweaning nonactivated PPs. These results suggest that PPs may have a unique organization and structure that enhance immune functions, allowing cells in LFs to have free access to adjacent LFs and egress smoothly from PPs to the periphery upon stimulation after weaning.

  4. Broad specificity of monoclonal IgA (TEPC15-IgA) for enteric bacteria via phosphorylcholine-mediated interaction.

    Saeka Koyama, Kaori Ito, Katsuki Usami, Shino Wada, Tsukasa Yamashita, Wakako Ikeda-Ohtsubo, Haruki Kitazawa, Ryota Hirakawa, Jahidul Islam, Mutsumi Furukawa, Tomonori Nochi

    The Journal of veterinary medical science　2024/06/04

    DOI： 10.1292/jvms.23-0441 　

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    Immunoglobulin A (IgA) is notable for its broad specificity toward multiple bacteria. Phosphorylcholine (PC) plays a role in the infection of pathogenic bacteria carrying PC and in the induction of IgA responses in the host immune system. The commercially available mouse monoclonal IgA, TEPC15-IgA, is a distinctive antibody with specificity for PC, warranting further exploration of its response to PC-bearing enteric bacteria. In this study, using 17 different enteric bacteria, including 3 aerobic and 14 anerobic bacteria that could be cultured in vitro, we confirmed that TEPC15-IgA recognizes 4 bacterial species: Lactobacillus taiwanensis, Limosilactobacillus frumenti, Streptococcus infantis, and Escherichia coli, although reactivity varied. Interestingly, TEPC15-IgA did not react with four of six Lactobacillus species used. Moreover, distinct target molecules associated with PC in L. taiwanensis and L. frumenti were evident, differing in molecular weight. These findings suggest that the natural generation of PC-specific IgA could prevent PC-mediated infections and potentially facilitate the formation of a microflora rich in indigenous bacteria with PC, particularly in the gastrointestinal tract.

  5. Identification of four genes responsible for antimicrobial resistance of MEL-B against S. aureus

    Shinya Yamauchi, So Shimoda, Akio Kawahara, Tomohiro Sugahara, Shuhei Yamamoto, Masao Kitabayashi, Atsushi Sogabe, Christine A. Jansen, Ryuta Tobe, Ryota Hirakawa, Jahidul Islam, Mutsumi Furukawa, Hiroshi Yoneyama, Tomonori Nochi

    Biochemical and Biophysical Research Communications　149566-149566　2024/01

    Publisher: Elsevier BV

    DOI： 10.1016/j.bbrc.2024.149566 　

    ISSN： 0006-291X

  6. Development of a rational framework for the therapeutic efficacy of fecal microbiota transplantation for calf diarrhea treatment

    Jahidul Islam, Masae Tanimizu, Yu Shimizu, Yoshiaki Goto, Natsuki Ohtani, Kentaro Sugiyama, Eriko Tatezaki, Masumi Sato, Eiji Makino, Toru Shimada, Chise Ueda, Ayumi Matsuo, Yoshihisa Suyama, Yoshifumi Sakai, Mutsumi Furukawa, Katsuki Usami, Hiroshi Yoneyama, Hisashi Aso, Hidekazu Tanaka, Tomonori Nochi

    Microbiome　10　(1)　2022/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1186/s40168-021-01217-4 　

    eISSN： 2049-2618

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    <title>Abstract</title><sec> <title>Background</title> Establishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection. In this study, the underlying factors of successful and unsuccessful FMT treatment cases are elucidated, and the potential markers for predicting successful FMT are identified using fecal metagenomics via 16S rRNA gene sequencing, fecal metabolomics via capillary electrophoresis time-of-flight mass spectrometry, and machine learning approaches. </sec><sec> <title>Results</title> Specifically, 20 FMT treatment cases, in which feces from healthy donors were intrarectally transferred into recipient diarrheal calves, were conducted with a success rate of 70%. <italic>Selenomonas</italic> was identified as a microorganism genus that showed significant donor–recipient compatibility in successful FMT treatments. A strong positive correlation between the microbiome and metabolome data, which is a prerequisite factor for FMT success, was confirmed by Procrustes analysis in successful FMT (<italic>r</italic> = 0.7439, <italic>P</italic> = 0.0001). Additionally, weighted gene correlation network analysis confirmed the positively or negatively correlated pairs of bacterial taxa (family <italic>Veillonellaceae</italic>) and metabolomic features (i.e., amino acids and short-chain fatty acids) responsible for FMT success. Further analysis aimed at establishing criteria for donor selection identified the genus <italic>Sporobacter</italic> as a potential biomarker in successful donor selection. Low levels of metabolites, such as glycerol 3-phosphate, dihydroxyacetone phosphate, and isoamylamine, in the donor or recipients prior to FMT, are predicted to facilitate FMT. </sec><sec> <title>Conclusions</title> Overall, we provide the first substantial evidence of the factors related to FMT success or failure; these findings could improve the design of future microbial therapeutics for treating diarrhea in calves. </sec>

  7. Roles of mannosylerythritol lipid-B components in antimicrobial activity against bovine mastitis-causing Staphylococcus aureus. International-journal

    Shinya Yamauchi, Mutsumi Furukawa, Akio Kawahara, Tomohiro Sugahara, Shuhei Yamamoto, Masao Kitabayashi, Atsushi Sogabe, So Shimoda, Eiji Hata, Kouichi Watanabe, Hiroshi Yoneyama, Hisashi Aso, Tomonori Nochi

    World journal of microbiology & biotechnology　38　(3)　54-54　2022/02/12

    DOI： 10.1007/s11274-022-03243-2 　

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    Mannosylerythritol lipid-B (MEL-B), which comprises ester-bonded hydrophilic ME and hydrophobic fatty acids, is a bio-surfactant with various unique properties, including antimicrobial activity against most gram-positive bacteria. The gram-positive Staphylococcus aureus is a causative pathogen of dairy cattle mastitis, which results in considerable economic loss in the dairy industry. Here, we demonstrate the efficacy of MEL-B as a disinfectant against bovine-derived S. aureus and elucidate a mechanism of action of MEL-B in the inhibition of bacterial growth. The growth of bovine mastitis causative S. aureus BM1006 was inhibited when cultured with MEL-B above 10 ppm. The activity of MEL-B required fatty acids (i.e., caprylic and myristoleic acids) as ME, the component of MEL-B lacking fatty acids, did not inhibit the growth of S. aureus even at high concentrations. Importantly, ME-bound fatty acids effectively inhibited the growth of S. aureus when compared with free fatty acids. Specifically, the concentrations of ME-bound fatty acids and free caprylic and myristoleic acids required to inhibit the growth of S. aureus were 10, 1442, and 226 ppm, respectively. The involvement of ME in the antimicrobial activity of MEL-B was confirmed by digestion of MEL-B with alkali, which dissociated ME and fatty acids. These results indicated that a mechanism of action of MEL-B in inhibiting the growth of S. aureus could be explained by the effective transporting of antimicrobial fatty acids to the bacterial surface via hydrophilic ME.

  8. Differential expression of CD11c defines two types of tissue-resident macrophages with different origins in steady-state salivary glands. International-journal

    Lu Lu, Toshinobu Kuroishi, Yukinori Tanaka, Mutsumi Furukawa, Tomonori Nochi, Shunji Sugawara

    Scientific reports　12　(1)　931-931　2022/01/18

    DOI： 10.1038/s41598-022-04941-5 　

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    Gland macrophages are primed for gland development and functions through interactions within their niche. However, the phenotype, ontogeny, and function of steady-state salivary gland (SG) macrophages remain unclear. We herein identified CD11c+ and CD11c- subsets among CD64+ macrophages in steady-state murine SGs. CD11c- macrophages were predominant in the SGs of embryonic and newborn mice and decreased with advancing age. CD11c+ macrophages were rarely detected in the embryonic period, but rapidly expanded after birth. CD11c+, but not CD11c-, macrophage numbers decreased in mice treated with a CCR2 antagonist, suggesting that CD11c+ macrophages accumulate from bone marrow-derived progenitors in a CCR2-dependent manner, whereas CD11c- macrophages were derived from embryonic progenitors in SGs. CD11c+ and CD11c- macrophages strongly expressed colony-stimulating factor (CSF)-1 receptor, the injection of an anti-CSF-1 receptor blocking antibody markedly reduced both subsets, and SGs strongly expressed CSF-1, indicating the dependency of SG resident macrophage development on CSF-1. The phagocytic activity of SG macrophages was extremely weak; however, the gene expression profile of SG macrophages indicated that SG macrophages regulate gland development and functions in SGs. These results suggest that SG CD11c+ and CD11c- macrophages are developed and instructed to perform SG-specific functions in steady-state SGs.

  9. The gut microbiota induces Peyer’s-patch-dependent secretion of maternal IgA into milk

    Katsuki Usami, Kanae Niimi, Ayumi Matsuo, Yoshihisa Suyama, Yoshifumi Sakai, Shintaro Sato, Kohtaro Fujihashi, Hiroshi Kiyono, Saeka Uchino, Mutsumi Furukawa, Jahidul Islam, Kaori Ito, Taiki Moriya, Yutaka Kusumoto, Michio Tomura, Russell C. Hovey, Junichi Sugawara, Hiroshi Yoneyama, Haruki Kitazawa, Kouichi Watanabe, Hisashi Aso, Tomonori Nochi

    Cell Reports　36　(10)　109655-109655　2021/09

    Publisher: Elsevier BV

    DOI： 10.1016/j.celrep.2021.109655 　

    ISSN： 2211-1247

  10. 出生直後のブタ回腸パイエル板の形態形成および機能成熟に関する組織学的研究

    古川 睦実, 伊藤 駿, 鈴木 俊一, 淵本 大一郎, 大西 彰, 渡邊 康一, 麻生 久, 野地 智法

    日本獣医学会学術集会講演要旨集　163回　178-178　2020/10

    Publisher: (公社)日本獣医学会

    ISSN： 1347-8621

  11. Elucidation of the Effects of a Current X-SCID Therapy on Intestinal Lymphoid Organogenesis Using an In Vivo Animal Model. International-journal

    Tomonori Nochi, Shunichi Suzuki, Shun Ito, Shotaro Morita, Mutsumi Furukawa, Daiichiro Fuchimoto, Yoji Sasahara, Katsuki Usami, Kanae Niimi, Osamu Itano, Minoru Kitago, Sachiko Matsuda, Ayumi Matsuo, Yoshihisa Suyama, Yoshifumi Sakai, Guoyao Wu, Fuller W Bazer, Kouichi Watanabe, Akira Onishi, Hisashi Aso

    Cellular and molecular gastroenterology and hepatology　10　(1)　83-100　2020

    DOI： 10.1016/j.jcmgh.2020.01.011 　

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    BACKGROUND & AIMS: Organ-level research using an animal model lacking Il2rg, the gene responsible for X-linked severe combined immunodeficiency (X-SCID), is clinically unavailable and would be a powerful tool to gain deeper insights into the symptoms of patients with X-SCID. METHODS: We used an X-SCID animal model, which was first established in our group by the deletion of Il2rg gene in pigs, to understand the clinical signs from multiple perspectives based on pathology, immunology, microbiology, and nutrition. We also treated the X-SCID pigs with bone marrow transplantation (BMT) for mimicking a current therapeutic treatment for patients with X-SCID and investigated the effect at the organ-level. Moreover, the results were confirmed using serum and fecal samples collected from patients with X-SCID. RESULTS: We demonstrated that X-SCID pigs completely lacked Peyer's patches (PPs) and IgA production in the small intestine, but possessed some dysfunctional intestinal T and B cells. Another novel discovery was that X-SCID pigs developed a heterogeneous intestinal microflora and possessed abnormal plasma metabolites, indicating that X-SCID could be an immune disorder that affects various in vivo functions. Importantly, the organogenesis of PPs in X-SCID pigs was not promoted by BMT. Although a few isolated lymphoid follicles developed in the small intestine of BMT-treated X-SCID pigs, there was no evidence that they contributed to IgA production and microflora formation. Consistently, most patients with X-SCID who received BMT possessed abnormal intestinal immune and microbial environments regardless of the presence of sufficient serum IgG. CONCLUSIONS: These results indicate that the current BMT therapies for patients with X-SCID may be insufficient to induce the organogenesis of intestinal lymphoid tissues that are associated with numerous functions in vivo.

  12. Organogenesis of Ileal Peyer's Patches Is Initiated Prenatally and Accelerated Postnatally With Comprehensive Proliferation of B Cells in Pigs. International-journal

    Mutsumi Furukawa, Shun Ito, Shunichi Suzuki, Daiichiro Fuchimoto, Akira Onishi, Kanae Niimi, Katsuki Usami, Guoyao Wu, Fuller W Bazer, Kouetsu Ogasawara, Kouichi Watanabe, Hisashi Aso, Tomonori Nochi

    Frontiers in immunology　11　604674-604674　2020

    DOI： 10.3389/fimmu.2020.604674 　

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    Morphogenesis and differentiation of organs is required for subsequent functional maturation. The morphological features of Peyer's patches vary among species. In pigs, they develop extensively in the ileum as ileal Peyer's patches (IPPs). However, the role of IPPs in the porcine immune system remains to be elucidated because of a lack of complete understanding of IPP organogenesis. Results of the present study revealed that development of porcine IPPs is initiated prenatally between embryonic days 76 and 91. The process of IPP organogenesis is concomitant with increased transcriptional patterns of CXCL13 and CCL19. IPPs undergo further development postnatally by forming central, marginal, and subepithelial zones. Importantly, a large number of proliferating B cells and apoptotic cells are found in porcine IPPs postnatally, but not prenatally. The expression level of IgM in proliferating B cells depends on the zone in which distinct B cells are separately localized after birth. Specifically, IgM+ cells are predominantly found in the central zone, whereas IgM-/low cells are abundant in the marginal zone. Importantly, the cellular feature of IPPs differs from that of mesenteric lymph nodes (MLNs) where such distinct zones are not formed both prenatally and postnatally. Our findings suggest that IPPs (not MLNs) in postnatal pigs are involved in complementing functions of the primary lymphoid tissue that promotes the differentiation and maturation of B cells.

  13. IL-2Rg欠損が免疫・微生物・代謝系に与える影響とX-SCIDブタへの胎生期造血幹細胞移植の有用性評価

    伊藤 駿, 鈴木 俊一, 淵本 大一郎, 大西 彰, 板野 理, 北郷 実, 松田 祐子, 盛田 彰太郎, 古川 睦実, 新實 香奈枝, 宇佐美 克紀, 渡邊 康一, 麻生 久, 野地 智法

    日本畜産学会大会講演要旨集　125回　124-124　2019/03

    Publisher: (公社)日本畜産学会

    ISSN： 1342-4688

  14. Development of immune and microbial environments is independently regulated in the mammary gland

    K. Niimi, K. Usami, Y. Fujita, M. Abe, M. Furukawa, Y. Suyama, Y. Sakai, M. Kamioka, N. Shibata, E. J. Park, S. Sato, H. Kiyono, H. Yoneyama, H. Kitazawa, K. Watanabe, T. Nochi, H. Aso

    Mucosal Immunology　11　(3)　643-653　2018/05/01

    DOI： 10.1038/mi.2017.90 　

    ISSN： 1933-0219

    eISSN： 1935-3456

  15. ブタにおける二次リンパ組織の形態形成機序の解明

    古川 睦実, 伊藤 駿, 鈴木 俊一, 淵本 大一郎, 渡邊 康一, 麻生 久, 野地 智法

    日本畜産学会大会講演要旨集　124回　115-115　2018/03

    Publisher: (公社)日本畜産学会

    ISSN： 1342-4688

  16. Identification of a novel mechanism of action of bovine IgG antibodies specific for Staphylococcus aureus. International-journal

    Mutsumi Furukawa, Hiroshi Yoneyama, Eiji Hata, Hidetomo Iwano, Hidetoshi Higuchi, Tasuke Ando, Mika Sato, Tomohito Hayashi, Yoshio Kiku, Yuya Nagasawa, Kanae Niimi, Katsuki Usami, Kumiko Ito, Kouichi Watanabe, Tomonori Nochi, Hisashi Aso

    Veterinary research　49　(1)　22-22　2018/02/26

    DOI： 10.1186/s13567-018-0517-y 　

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    Staphylococcus aureus is a major pathogen that causes subclinical mastitis associated with huge economic losses to the dairy industry. A few vaccines for bovine mastitis are available, and they are expected to induce the production of S. aureus-specific antibodies that prevent bacterial adherence to host cells or promote opsonization by phagocytes. However, the efficacy of such vaccines are still under debate; therefore, further research focusing on improving the current vaccines by seeking additional mechanisms of action is required to reduce economic losses due to mastitis in the dairy industry. Here, we generated S. aureus-specific bovine IgG antibodies (anti-S. aureus) that directly inhibited bacterial growth in vitro. Inhibition depended on specificity for anti-S. aureus, not the interaction between Protein A and the fragment crystallizable region of the IgG antibodies or bacterial agglutination. An in vitro culture study using S. aureus strain JE2 and its deletion mutant JE2ΔSrtA, which lacks the gene encoding sortase A, revealed that the effect of anti-S. aureus was sortase-A-independent. Sortase A is involved in the synthesis of cell-wall-associated proteins. Thus, other surface molecules, such as membrane proteins, cell surface polysaccharides, or both, may trigger the inhibition of bacterial growth by anti-S. aureus. Together, our findings contribute insights into developing new strategies to further improve the available mastitis vaccine by designing a novel antigen on the surface of S. aureus to induce inhibitory signals that prevent bacterial growth.

  17. 二次リンパ組織の形態形成に関するブタ胎仔を用いた組織学的研究

    古川 睦実, 伊藤 駿, 盛田 彰太郎, 鈴木 俊一, 淵本 大一郎, 中井 美智子, 大西 彰, 新實 香奈枝, 宇佐美 克紀, 佐々木 志保, 渡邊 康一, 麻生 久, 野地 智法

    日本獣医学会学術集会講演要旨集　160回　309-309　2017/08

    Publisher: (公社)日本獣医学会

    ISSN： 1347-8621

  18. X-SCIDモデルブタ(IL2Rg欠損ブタ)の各種臓器内に認められるT細胞およびB細胞分布に関する組織学的研究

    伊藤 駿, 古川 睦実, 盛田 彰太郎, 鈴木 俊一, 淵本 大一郎, 中井 美智子, 大西 彰, 新實 香奈枝, 宇佐美 克紀, 佐々木 志保, 渡邊 康一, 麻生 久, 野地 智法

    日本獣医学会学術集会講演要旨集　160回　373-373　2017/08

    Publisher: (公社)日本獣医学会

    ISSN： 1347-8621

  19. 黄色ブドウ球菌特異的IgG抗体はSortase A非依存的に細胞増殖を阻害する(S. aureus-specific IgG antibodies inhibit the bacterial growth in a Sortase A independent manner)

    古川 睦実, 米山 裕, 秦 英司, 安藤 太助, 林 智人, 菊 佳男, 長澤 裕哉, 渡邊 康一, 麻生 久, 野地 智法

    日本細菌学雑誌　72　(1)　65-65　2017/02

    Publisher: 日本細菌学会

    ISSN： 0021-4930

    eISSN： 1882-4110

  20. 乳腺を標的としたIgA誘導型粘膜ワクチン開発を目指した学術基盤の形成

    新實 香奈枝, 阿部 未来, 藤田 勇気, 盛田 彰太郎, 古川 睦実, 宇佐美 克紀, 朴 恩正, 佐藤 慎太郎, 清野 宏, 渡邊 康一, 麻生 久, 野地 智木

    日本畜産学会大会講演要旨集　121回　148-148　2016/03

    Publisher: (公社)日本畜産学会

    ISSN： 1342-4688

Show all ︎Show first 5

Misc. 8

  1. 乳汁IgAが有する腸内微生物に対する特異性評価

    内野紗江佳, 宇佐美克己, 新實香奈枝, 古川睦実, 野地智法

    東北畜産学会報　71　(2)　2021

    ISSN： 1341-626X

  2. 乳汁IgAの産生制御因子としてのPolymeric immunoglobulin Receptor(PigR)の機能解明

    伊東加織, 内野紗江佳, 宇佐美克己, 古川睦実, 松本敬, 南野昌信, 麻生久, 野地智法

    日本畜産学会大会講演要旨　129th　2021

    ISSN： 1342-4688

  3. 初乳中自然免疫因子Serum Amyloid Aの同定とその作用標的

    内野紗江佳, 宇佐美克紀, 佐々木志保, 新實香奈枝, 古川睦実, 渡邊康一, 麻生久, 野地智法

    日本獣医学会学術集会講演要旨集　163rd　2020

    ISSN： 1347-8621

  4. 乳汁中のIgA抗体産生を促す腸内微生物の免疫・微生物学的意義

    宇佐美克紀, 新實香奈枝, 古川睦実, 馬場柚里, 内野紗江佳, 山内清哉, 渡邊康一, 麻生久, 野地智法

    日本獣医学会学術集会講演要旨集　162nd　2019

    ISSN： 1347-8621

  5. 二次リンパ組織の形態形成に関するブタ胎仔を用いた組織学的研究

    古川 睦実, 伊藤 駿, 盛田 彰太郎, 鈴木 俊一, 淵本 大一郎, 中井 美智子, 大西 彰, 新實 香奈枝, 宇佐美 克紀, 佐々木 志保, 渡邊 康一, 麻生 久, 野地 智法

    日本獣医学会学術集会講演要旨集　160回　309-309　2017/08

    Publisher: (公社)日本獣医学会

    ISSN： 1347-8621

  6. X-SCIDモデルブタ(IL2Rg欠損ブタ)の各種臓器内に認められるT細胞およびB細胞分布に関する組織学的研究

    伊藤 駿, 古川 睦実, 盛田 彰太郎, 鈴木 俊一, 淵本 大一郎, 中井 美智子, 大西 彰, 新實 香奈枝, 宇佐美 克紀, 佐々木 志保, 渡邊 康一, 麻生 久, 野地 智法

    日本獣医学会学術集会講演要旨集　160回　373-373　2017/08

    Publisher: (公社)日本獣医学会

    ISSN： 1347-8621

  7. 黄色ブドウ球菌(SA)の死菌接種によって産生されるポリクローナル抗体はSAに対する増殖阻害効果を有する

    古川 睦実, 米山 裕, 秦 英司, 岩野 英知, 樋口 豪紀, 安藤 太助, 佐藤 美佳, 林 智人, 菊 佳男, 長澤 裕哉, 新實 香奈枝, 宇佐美 克紀, 佐々木 志保, 伊藤 駿, 渡邊 康一, 麻生 久, 野地 智法

    家畜感染症学会誌　5　(4)　181-181　2016/12

    Publisher: 家畜感染症学会誌編集委員会

    ISSN： 2186-7208

  8. 黄色ブドウ球菌のin vitroでの増殖阻害を可能にするウシポリクローナル抗体の作製

    古川睦実, 米山裕, 秦英司, 岩野英知, 樋口豪紀, 安藤太助, 佐藤美佳, 林智人, 菊佳男, 長澤裕哉, 新實香奈枝, 宇佐美克紀, 佐々木志保, 伊藤駿, 渡邊康一, 麻生久, 野地智法

    東北畜産学会報　66　(2)　27-27　2016/08/12

    Publisher: 東北畜産学会

    ISSN： 1341-626X

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Research Projects 5

  1. 仔のパイエル板発達における乳汁抗体結合細菌の重要性の解明

    古川 睦実

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 若手研究

    Institution: 東北大学

    2025/04/01 - 2027/03/31

  2. Clustering of plasma cells for a comprehensive understanding of immune function in the mammary glands

    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

    2022/04/01 - 2026/03/31

  3. 鳥類の免疫学におけるパラダイムシフトによる鶏のB細胞分化に関する概念の再構築

    野地 智法, 古川 睦実

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2023/06/30 - 2025/03/31

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    本申請は、ニワトリ（鶏）の免疫機能に関するこれまでの研究成果をもとに、既存の鳥類の免疫学における概念を新たにすべく提案されている。ファブリキウス嚢は、B細胞の初期分化の場として、半世紀以上前に発見された鶏特有の臓器である。当時から現代に受け継がれている鶏免疫学の教科書には、孵化直後の雛のファブリキウス嚢を切除することで、鶏の抗体産生は完全に欠失すると記載されている。一方で、申請者はこれまでに、孵化直後の雛へのファブリキウス嚢摘出の影響は一時的であり、ファブリキウス嚢非存在下でも、成長とともに腸管を中心とした免疫機能が発達することを示してきた。特に、鶏腸管最大の免疫臓器である盲腸扁桃は、ファブリキウス嚢非存在下で働く免疫系の中枢であり、その理由として、ファブリキウス嚢を経由せずに、骨髄から盲腸扁桃へ直接遊走するB細胞が存在することを突き止めてきた。また、骨髄由来のそれらのB細胞は未熟であり、ファブリキウス嚢と同様に、盲腸扁桃で成熟B細胞に分化していることを見出してきた。これらの研究成果は、ファブリキウス嚢が絶対的な地位にある鳥類の免疫学に関する定説（パラダイム）を覆す、鶏のB細胞の新たな分化経路の存在を支持する一方で、目的 その意義を理解する必要性を強く示すものであった。そこで本研究では、鳥類の免疫学にパラダイムシフトをもたらすことで、盲腸扁桃におけるファブリキウス嚢依存的および非依存的なB細胞分化の実態を明らかにする。研究を通して、これまでに明らかにしてきたことは、ファブリキウス嚢非依存的（＝骨髄依存的）なB細胞は、CXCL12/CXCR4を介した細胞遊走機序により盲腸扁桃に遊走すること、また、ファブリキウス嚢および骨髄由来の双方のB細胞の盲腸扁桃への遊走を阻害することにより、腸管免疫（特にIgA産生）は著しい影響を受けることを示してきた。

  4. 『乳』を起点とした仔豚の腸管免疫発達機序の解明

    古川 睦実

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 若手研究

    Institution: 東北大学

    2023/04/01 - 2025/03/31

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    回腸パイエル板は出生時に最大の免疫臓器である。また、哺乳期間の前期・中期・後期および離乳後で、回腸パイエル板を構成している免疫細胞が大きく変化していると考えられる。そのため今年度は、シングルセルレベルでの解析を行うことで、哺乳期間から離乳後までの回腸パイエル板を構成する細胞の特徴を明らかにすることを目的とした。 １週齢、２週齢、３週齢、５週齢のブタから回腸パイエル板を採材し、細胞単離を行った。回腸パイエル板から単離した細胞を、Chromium Controller（10ｘ Genomics社）に供することで、一つ一つの細胞を識別するゲルビーズとPCR酵素が入ったエマルジョンを調整した。その後、調整したエマルジョンをインキュベーションし、反応後、精製した。さらに、cDNAを増幅した。加えて、得られたcDNAを最適なサイズに断片化し、A-tailingや各サンプルを識別するIndex配列を付加させ、反応後のcDNA libraryをHiSeq 2500 (illumina)を用いたシーケンシングに供した。 シーケンス後、Cell Rangerを用いてデータをFASTQ形式に変換し、マッピング、フィラリング、細胞ごとのバーコードのカウント、UMIのカウントを行った。また、レファレンスゲノムにはEnsenblから取得したSus scrofa 11.1を用いた。データ解析にはSeurat 4.3.0.1を使用し、データセットの上位2,000個の変動性の高い遺伝子を用いて主成分分析を行い、上位20個のPCを使用して次元削減を行った後、UMAPを用いて可視化した。 <BR> 今年得られた結果として、CD79A、CD79B、JCHAIN、IRF4、EBF1、BIRC5、GRP183、 PAX5、CD74、TNFRSF13Cが各時期でのB細胞を特徴づけるマーカーとなるといえた。

  5. 宿主免疫による黄色ブドウ球菌の増殖抑制を促す乳房炎ワクチン用新規抗原の探索

    古川 睦実

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 特別研究員奨励費

    Institution: 東北大学

    2019/04 - 2021/03

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    ウシ乳房炎は黄色ブドウ球菌などの病原微生物が引き起こす感染症であり、酪農現場に甚大な被害をもたらす。治療のための抗生物質の使用は乳汁の出荷停止や薬剤耐性菌の出現の原因となるため、薬剤に頼らない疾病防除が重要であり、特にワクチンの質の向上が必須である。先行研究では、既存の乳房炎ワクチンを模倣し、黄色ブドウ球菌(死菌)をウシに免疫することで産生される、黄色ブドウ球菌の様々な分子を認識する抗体の中で、黄色ブドウ球菌の増殖そのものを直接的に制御する、中和活性を有した抗体が含まれているか否かを検証してきた。その結果、黄色ブドウ球菌特異的ウシIgG抗体との共培養により、黄色ブドウ球菌のCFU数が有意に減少するという結果を得ていた。本研究の目的は黄色ブドウ球菌特異的ウシIgG抗体による黄色ブドウ球菌の増殖抑制に関与する抗原を同定し、ウシ乳房炎のワクチン抗原へと応用することであった。 今年度は、黄色ブドウ球菌特異的抗体（抗SA抗体）による増殖抑制効果が、抗体を構成する中で、どのような領域によって引き起こされるかを明らかにした。 IgG抗体はFabとFcの２つのフラグメントで構成され、抗体の特異性を決定する領域はFab領域に存在する。そこで、まず、抗SA抗体をFab断片とFc断片に切断するために、Pepsinで処理した。無処理、Buffer置換後（Pepsin処理前）、Pepsin処理後の抗SA抗体をSDS-PAGEに供することで、Pepsin処理により、Fab断片とFc断片に抗体が切断されたことを確認した。 次に、黄色ブドウ球菌を植菌した培地中に、抗SA抗体およびPepsin処理後の抗SA抗体を添加し、黄色ブドウ球菌に対する増殖抑制効果を検証した。その結果、Pepsin処理を行っても増殖抑制効果が確認され、抗SA抗体による増殖抑制効果がFab領域によるものであることが示された。