Details of the Researcher

PHOTO

Toshiya Takahashi
Section
Tohoku University Hospital
Job title
Senior Assistant Professor
Degree

  • M.D. (Tohoku University)

  • Ph.D.

Profile
皮膚科(乾癬、アトピー性皮膚炎、接触皮膚炎)、自然免疫、抗菌ペプチド

Research History 1

  • 2026/01 - Present
    Tohoku University　University Hospital　senior assistant professor

Research Interests 4

  • antimicrobial peptide

  • innate immunity

  • immunology

  • dermatology

Research Areas 1

  • Life sciences / Dermatology / immunology

Papers 36

  1. Long-Term Real-World Outcomes of Baricitinib in Severe Alopecia Areata: A 104-Week Retrospective Analysis From a Single Institute. International-journal

    Moyuka Wada-Irimada, Takehiro Takahashi, Mana Sekine, Toshiki Okazaki, Takuya Takahashi, Tomoko Chiba, Emi Yamazaki, Kosuke Shido, Toshiya Takahashi, Masato Mizuashi, Yoshihide Asano

    The Journal of dermatology　2025/06/20

    DOI： 10.1111/1346-8138.17829 　

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    Baricitinib, a Janus kinase inhibitor, demonstrated efficacy in achieving scalp hair regrowth in severe alopecia areata (AA). While short-term real-world data on its efficacy have been reported, long-term data remain limited. This retrospective observational study spanning 104 weeks analyzed clinical trajectories of 51 severe AA patients treated with baricitinib. Among them, 36 continued treatment for 104 weeks, with 55.6% achieving a SALT score of ≤ 20 and 72.2% achieving ≥ 30% improvement from baseline in SALT score (SALT30). Multivariate analysis identified female sex and disease duration < 4 years as significant predictors of response. Furthermore, patients with eyebrow or eyelash regrowth at 52 weeks had a higher likelihood of achieving long-term scalp hair regrowth. We identified a subgroup of markedly slow responders who achieved SALT30 between 52 and 104 weeks, many of whom had eyebrow or eyelash regrowth at 52 weeks. Baricitinib was well tolerated throughout the study period, with no serious long-term adverse effects. Our findings supported baricitinib's long-term efficacy and safety and suggested predictive factors for treatment responses in severe AA.

  2. Predictive factors for treatment responses to baricitinib in severe alopecia areata: A retrospective, multivariate analysis of 70 cases from a single center. International-journal

    Moyuka Wada-Irimada, Takehiro Takahashi, Mana Sekine, Toshiki Okazaki, Takuya Takahashi, Tomoko Chiba, Emi Yamazaki, Kosuke Shido, Toshiya Takahashi, Masato Mizuashi, Yoshihide Asano

    The Journal of dermatology　2025/01/27

    DOI： 10.1111/1346-8138.17641 　

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    Alopecia areata (AA) is a chronic, autoimmune skin disease characterized by non-scarring hair loss. Baricitinib, a Janus kinase inhibitor (JAKi), prevents hair loss and promotes hair regrowth by inhibiting the inflammatory Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway involved in cytotoxic T cell responses targeting hair follicles. The introduction of JAKi has transformed treatment against severe AA. However, treatment responses to JAKi are highly variable among patients, and the predictors of responsiveness remain insufficiently elucidated. This study aimed to identify independent predictive factors for the efficacy of baricitinib in patients with severe AA using multivariate analyses. A retrospective study was conducted on 70 severe AA patients who started baricitinib treatment at Tohoku University Hospital between July 2022 and August 2023. The primary outcome was the percentage of patients achieving a Severity of Alopecia Tool (SALT) score of ≤20 after 9 months of baricitinib treatment. Multivariate analysis assessed potential predictors of baricitinib treatment responses, including AA type, sex, age, disease duration, history of atopic dermatitis, intravenous methylprednisolone pulse (IVMP) therapy, and Clinician-Reported Outcome (ClinRO) measures for eyebrows and eyelashes. Achievement of a SALT score of ≤20 and SALT score improvement rates were used as objective variables in the multivariate analyses. Among the 70 patients completing 9 months of baricitinib treatment, 41% achieved a SALT score of ≤20. Multivariate analyses identified several independent predictors for positive outcomes, including shorter disease duration (≤4 years), history of IVMP, therapy SALT score of ≤95 at baricitinib initiation, and female sex. Further, we found differential response patterns based on AA type and sex. Specifically, AA type significantly influenced treatment responses, with ophiasis alopecia (OA) associated with the poorest improvement rate. In summary, the response to baricitinib in AA is significantly influenced by sex, AA type, disease duration, history of IVMP, and pre-treatment SALT score.

  3. A Potential Contribution of S100A11 to Skin Fibrosis and Pulmonary Involvement in Systemic Sclerosis. International-journal

    Takuya Takahashi, Takehiro Takahashi, Yuichiro Segawa, Tetsuya Ikawa, Hitoshi Terui, Toshiya Takahashi, Hayakazu Sumida, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    Experimental dermatology　34　(1)　e70026　2025/01

    DOI： 10.1111/exd.70026 　

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    Systemic sclerosis (SSc) is characterised by immune dysregulation, vasculopathy and fibrosis, driven by genetic and environmental factors. S100 proteins, which constitute a unique class of calcium-binding proteins, have been shown to be critically implicated in various inflammatory and fibrotic conditions. In this study, we investigated the possible involvement of S100A11 in SSc by examining its cutaneous expression and systemic serum levels, correlating them with key clinical parameters. First, we performed immunohistochemical (IHC) staining to examine S100A11 localisation in skin specimens from SSc patients and controls, and found that S100A11 was robustly expressed in SSc dermal fibroblasts. Analysis on the publicly available single-cell RNA-sequencing (scRNA-seq) data of SSc skin samples further confirmed that S100A11 was highly expressed in SSc dermal fibroblasts along with several key genes associated with cellular senescence. Finally, we evaluated serum levels of S100A11 in SSc patients and HCs using enzyme-linked immunosorbent assay (ELISA), and found that serum S100A11 levels were significantly elevated in diffuse cutaneous SSc (dcSSc) patients compared to controls. S100A11 serum levels in SSc patients were significantly correlated with modified Rodnan total skin thickness score and key parameters of SSc-related interstitial lung disease. Our data collectively suggested a potential pathophysiological role of S100A11 in the cutaneous and lung fibrosis associated with SSc, warranting further investigation into its functional roles in this disease.

  4. Case report: Nodular scleroderma successfully treated with tocilizumab. International-journal

    Takuya Takahashi, Takehiro Takahashi, Mai Ueki, Hitoshi Terui, Yuichiro Segawa, Tetsuya Ikawa, Toshiya Takahashi, Yumi Kambayashi, Yoshihide Asano

    International journal of rheumatic diseases　27　(5)　e15200　2024/05

    DOI： 10.1111/1756-185X.15200 　

  5. 診断に難渋した下肢extranodal NK/T-cell lymphoma,nasal typeの1例

    水芦 政人, 山本 悠, 赤井 紗彩, 高橋 隼也, 山崎 研志, 浅野 善英, 谷田 宗男, 市川 聡, 横山 寿行

    日本皮膚科学会雑誌　133　(4)　708-709　2023/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  6. The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors. International-journal

    Ryo Amagai, Toshiya Takahashi, Hitoshi Terui, Taku Fujimura, Kenshi Yamasaki, Setsuya Aiba, Yoshihide Asano

    International journal of molecular sciences　24　(1)　2023/01/03

    DOI： 10.3390/ijms24010875 　

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    An active form of cathelicidin antimicrobial peptide, LL-37, has immunomodulatory and stimulatory effects, though the specific pathways are not clear. The purpose of this study was to identify the cellular pathways by which LL-37 amplifies the inflammation induced by damage-associated molecular patterns (DAMPs). We performed DNA microarray, reverse transcription polymerase chain reaction, immunoblotting, and proximity ligation assays using cultured keratinocytes treated with LL-37 and/or the DAMP poly(I:C), a synthetic double-stranded RNA. In contrast to the combination of LL-37 and poly(I:C), LL-37 alone induced genes related to biological metabolic processes such as VEGFA and PTGS2 (COX-2). Inhibition of FPR2, a known receptor for cathelicidin, partially suppressed the induction of VEGFA and PTGS2. Importantly, VEGFA and PTGS2 induced by LL-37 alone were diminished by the knockdown of scavenger receptors including SCARB1 (SR-B1), OLR1 (SR-E1), and AGER (SR-J1). Moreover, LL-37 alone, as well as the combination of LL-37 and poly(I:C), showed proximity to the scavenger receptors, indicating that LL-37 acts via scavenger receptors and intermediates between them and poly(I:C). These results showed that the broad function of cathelicidin is generally dependent on scavenger receptors. Therefore, inhibitors of scavenger receptors or non-functional mock cathelicidin peptides may serve as new anti-inflammatory and immunosuppressive agents.

  7. 壊疽性膿皮症診療の手引き2022

    山本 俊幸, 山崎 研志, 山中 恵一, 小宮根 真弓, 川上 民裕, 山元 修, 金蔵 拓郎, 樋口 哲也, 高橋 隼也, 松島 由明, 菊池 信之, 壊疽性膿皮症診療の手引き作成委員会

    日本皮膚科学会雑誌　132　(6)　1415-1440　2022/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  8. Biologics modulate antinuclear antibodies, immunoglobulin E, and eosinophil counts in psoriasis patients. International-journal

    Riichiro Sugiura, Hitoshi Terui, Ryoko Shimada-Omori, Emi Yamazaki, Kenichiro Tsuchiyama, Toshiya Takahashi, Setsuya Aiba, Kenshi Yamasaki

    The Journal of dermatology　48　(11)　1739-1744　2021/11

    DOI： 10.1111/1346-8138.16102 　

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    Psoriasis is a chronic disease centered on tumor necrosis factor (TNF), interleukin (IL)-23, and IL-17 axis. While psoriasis patients benefit from biologics targeting TNF, IL-17s, and IL-23 nowadays, suppression of these molecules could modulate the balances of immune systems. However, the incidence of autoimmune disease and T-helper 2 reaction during biologic treatments for psoriasis patients is not well documented. We retrospectively examined antinuclear antibody (ANA), eosinophil counts, and immunoglobulin E (IgE) levels for psoriasis patients who underwent biologic treatments in our dermatology clinic from June 10, 2010 to January 29, 2020. A cumulative total of 199 biologic treatments were performed for a total of 128 psoriasis patients. Compared to the non-biologic group of 109 psoriasis patients who received non-biologic treatment, patients treated with infliximab showed more incidents of high ANA (14%, p = 0.039) and high eosinophils (14%, p = 0.021). The use of brodalumab increased incidents of high eosinophils (21%, p = 0.005) but did not affect increase in ANA and IgE. The increase in high IgE level was observed significantly more during the use of risankizumab (15%, p = 0.011). Methotrexate was the most frequently used concomitant systemic treatment, but methotrexate did not affect ANA, eosinophil counts, and IgE levels. Since the biologics for psoriasis treatment modulate the balance of T-helper cells, careful observation is required to detect unexpected changes of systemic immune conditions under biologic treatments.

  9. Body mass index, HbA1c and serum C-reactive protein are predictors of secondary failure in infliximab continuance for Japanese psoriasis patients: A hospital-based retrospective case-control study. International-journal

    Hitoshi Terui, Masayuki Asano, Ryoko Shimada-Omori, Kenichiro Tsuchiyama, Toshiya Takahashi, Mei Nasu-Tamabuchi, Akiko Hagiwara-Takita, Yoshiyuki Kusakari, Tomoyuki Ohtani, Setsuya Aiba, Kenshi Yamasaki

    The Journal of dermatology　48　(11)　1719-1723　2021/11

    DOI： 10.1111/1346-8138.16096 　

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    Biologics has had a great impact on psoriasis treatment as well as the life of psoriasis patients. Infliximab (IFX), one of the biologics targeting tumor necrosis factor (TNF), is the first of the biologics introduced to Japanese psoriasis patients. Many patients had benefits of IFX from initial applications and sustained remission of skin lesions and arthritis. Some, however, fall into so-called secondary failure, in which patients become less responsive to IFX when the treatment is repeated. The mechanism of secondary failure and the background of patients with secondary failure have not been completely elucidated. To address this issue, we retrospectively evaluated psoriasis patients treated with IFX in our department. In this retrospective, single-center, case-control study based on the clinical record, a total of 34 patients were enrolled. We excluded 7 patients who discontinued IFX because of adverse events of IFX. We divided other 27 patients into two groups; 16 patients who kept using IFX (Continuance group); and 11 patients who switched to other treatments (Discontinuance group). Among various clinical features, body mass index (BMI), HbA1c, and serum CRP level were significantly higher in the Discontinuance group than the Continuance group. The results indicated that these three clinical features of BMI, HbA1c and serum CRP level before treatment are the predictors of successful IFX treatment and suggest that improvement of metabolic conditions contributes to avoiding secondary failure and discontinuance of IFX.

  10. Optimization of the IL-2 Luc assay for immunosuppressive drugs: a novel in vitro immunotoxicity test with high sensitivity and predictivity. International-journal

    Yutaka Kimura, Hitoshi Terui, Chizu Fujimura, Ryo Amagai, Toshiya Takahashi, Setsuya Aiba

    Archives of toxicology　95　(8)　2755-2768　2021/08

    DOI： 10.1007/s00204-021-03101-4 　

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    We have reported that the IL-2 Luc assay can detect the effects of chemicals on IL-2 promoter activity by using a dual reporter cell line, 2H4 cells that measure IL-2 promoter-driven luciferase activity (IL2LA) and GAPDH promoter-driven luciferase activity (GAPLA). Since the IL-2 Luc assay cannot detect immunosuppressive drugs that are antimitotic towards rapidly proliferating cells, we attempted to establish a new assay to detect these chemicals by taking advantage of the dual reporter cell properties of 2H4 cells. We first determined the optimal incubation time with drugs and the seeding cell density, and confirmed that the change in GAPLA and IL2LA levels reflects the change in cell count and IL-2 production of 2H4 cells after drug treatment. We designed the IL-2 luciferase lymphotoxicity test (IL-2 Luc LTT) to detect the antimitotic effects of chemicals by modifying the protocol and criteria of the IL-2 Luc assay. To determine the performance of the IL-2 Luc LTT and that of the combination of the IL-2 Luc LTT and the IL-2 Luc assay, we examined 46 drugs: 19 immunosuppressive drugs with different mechanisms of action, 12 anti-cancer drugs, and 15 non-immunosuppressive drugs. The performances of the IL-2 Luc LTT, the IL-2 Luc assay and their combination were 43.3%, 61.3%, and 93.3%, respectively, for sensitivity, 84.6%, 53.3%, and 50.0%, respectively, for specificity, and 55.8%, 58.7%, and 79.5%, respectively, for accuracy. These results demonstrated that the combination of these two assays is promising for the detection of immunosuppressive drugs with different mechanisms of action.

  11. Psoriatic arthritis with skin lesions localized to the scalp: A case report.

    Tetsuya Akaishi, Kenshi Yamasaki, Yu Mori, Toshiya Takahashi, Takuya Izumiyama, Hitoshi Terui, Michiaki Abe, Shin Takayama, Setsuya Aiba, Tadashi Ishii

    Journal of general and family medicine　21　(6)　264-267　2020/11

    DOI： 10.1002/jgf2.358 　

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    A 66-year-old man with a 2-year history of suspected scalp eczema with excessive dandruff developed painful swollen joints in the extremities. Four months after developing polyarthritis and polydactylitis, eczema gradually spread to the face. He was referred to our hospital for intractable scalp and facial eczema and polyarthritis. Based on the appearance of the head and facial skin lesions, psoriasis was suspected. Treatment with apremilast (a phosphodiesterase-4-inhibitor) was initiated, which swiftly alleviated the skin lesions. The joint deformities persisted, but the pain in the joints disappeared. This case implies that psoriatic arthritis should be suspected even if psoriatic skin lesions are localized to the scalp.

  12. Psoriasis and Antimicrobial Peptides. International-journal

    Toshiya Takahashi, Kenshi Yamasaki

    International journal of molecular sciences　21　(18)　2020/09/16

    DOI： 10.3390/ijms21186791 　

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    Psoriasis is a systemic inflammatory disease caused by crosstalk between various cells such as T cells, neutrophils, dendritic cells, and keratinocytes. Antimicrobial peptides (AMPs) such as β-defensin, S100, and cathelicidin are secreted from these cells and activate the innate immune system through various mechanisms to induce inflammation, thus participating in the pathogenesis of psoriasis. In particular, these antimicrobial peptides enhance the binding of damage-associated molecular patterns such as self-DNA and self-RNA to their receptors and promote the secretion of interferon from activated plasmacytoid dendritic cells and keratinocytes to promote inflammation in psoriasis. Neutrophil extracellular traps (NETs), complexes of self-DNA and proteins including LL-37 released from neutrophils in psoriatic skin, induce Th17. Activated myeloid dendritic cells secrete a mass of inflammatory cytokines such as IL-12 and IL-23 in psoriasis, which is indispensable for the proliferation and survival of T cells that produce IL-17. AMPs enhance the production of some of Th17 and Th1 cytokines and modulate receptors and cellular signaling in psoriasis. Inflammation induced by DAMPs, including self-DNA and RNA released due to microinjuries or scratches, and the enhanced recognition of DAMPs by AMPs, may be involved in the mechanism underlying the Köbner phenomenon in psoriasis.

  13. Increased expression of dermal LL37 may trigger migration of CCR7+ regulatory T cells in extramammary Paget's disease. International-journal

    Chunbing Lyu, Taku Fujimura, Ryo Amagai, Kentaro Ohuchi, Yota Sato, Kayo Tanita, Shigeto Matsushita, Yasuhiro Fujisawa, Atsushi Otsuka, Yuki Yamamoto, Toshiya Takahashi, Setsuya Aiba

    Journal of dermatological science　99　(1)　65-68　2020/07

    DOI： 10.1016/j.jdermsci.2020.05.003 　

  14. IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation

    Saaya Yoshida, Taku Fujimura, Kentaro Ohuchi, Yumi Kambayashi, Yuichiro Segawa, Emi Yamazaki, Hisayuki Tono, Toshiya Takahashi, Kenichiro Tsuchiyama, Setsuya Aiba

    Case Reports in Oncology　13　(1)　462-467　2020

    Publisher: S. Karger AG

    DOI： 10.1159/000506975 　

    ISSN： 1662-6575

  15. Perifolliculitis capitis abscedens et suffodiens treatment with tumor necrosis factor inhibitors: A case report and review of published cases Peer-reviewed

    Toshiya Takahashi, Kenshi Yamasaki, Hitoshi Terui, Ryoko Omori, Kenichiro Tsuchiyama, Taku Fujimura, Setsuya Aiba

    The Journal of Dermatology　46　(9)　802-807　2019/09

    Publisher: Wiley

    DOI： 10.1111/1346-8138.14998 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  16. Severe rhabdomyolysis developing in an advanced melanoma patient treated by pembrolizumab followed by dabrafenib trametinib combined therapy. Peer-reviewed

    Irimada M, Fujimura T, Kambayashi Y, Tsukada A, Takahashi T, Hashimoto A, Aiba S

    The Journal of dermatology　46　(7)　e256-e258　2019/07

    DOI： 10.1111/1346-8138.14778 　

    ISSN： 0385-2407

  17. Successful treatment of unresectable recurrent programmed death ligand 1 moderately-expressing malignant melanoma of the nasal cavity with pembrolizumab monotherapy. Peer-reviewed

    Fujimura T, Kambayashi Y, Sato Y, Tanita K, Tono H, Lyu C, Takahashi T, Hashimoto A, Aiba S

    The Journal of dermatology　46　(7)　e260　2019/07

    DOI： 10.1111/1346-8138.14786 　

    ISSN： 0385-2407

  18. Chronkhite-Canada syndromeの2例

    志藤 光介, 高橋 隼也, 山崎 研志, 相場 節也

    日本皮膚科学会雑誌　129　(3)　399-399　2019/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  19. Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay Peer-reviewed

    Yutaka Kimura, Chizu Fujimura, Yumiko Ito, Toshiya Takahashi, Hitoshi Terui, Setsuya Aiba

    Archives of Toxicology　92　(6)　2043-2054　2018/06/01

    Publisher: Springer Verlag

    DOI： 10.1007/s00204-018-2199-7 　

    ISSN： 1432-0738 0340-5761

    eISSN： 1432-0738

  20. Cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors. Peer-reviewed

    Takahashi T, Kulkarni NN, Lee EY, Zhang LJ, Wong GCL, Gallo RL

    Scientific reports　8　(1)　4032　2018/03

    DOI： 10.1038/s41598-018-22409-3 　

  21. Crystallinity of Double-Stranded RNA-Antimicrobial Peptide Complexes Modulates Toll-Like Receptor 3-Mediated Inflammation. International-journal Peer-reviewed

    Lee EY, Takahashi T, Curk T, Dobnikar J, Gallo RL, Wong GCL

    ACS nano　11　(12)　12145-12155　2017/12

    DOI： 10.1021/acsnano.7b05234 　

    ISSN： 1936-0851

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    Double-stranded RNA (dsRNA) induces production of pro-inflammatory cytokines in normal human epidermal keratinocytes (NHEK) by specific binding to endosomal Toll-like receptor-3 (TLR3). Recently, it has been shown that hyperactivation of TLR3 in psoriatic keratinocytes by dsRNA can occur in the presence of human antimicrobial peptide (AMP) LL37. Here, we combine synchrotron X-ray scattering, microscopy, computer simulations, and measurements of NHEK cytokine production to elucidate a previously unanticipated form of specific molecular pattern recognition. LL37 and similar α-helical AMPs can form pro-inflammatory nanocrystalline complexes with dsRNA that are recognized by TLR3 differently than dsRNA alone. dsRNA complexes that activate IL-6 production in NHEK and those that do not are both able to enter cells and co-localize with TLR3. However, the crystallinity of these AMP-dsRNA complexes, specifically the geometric spacing between parallel dsRNA and the repeat number of ordered dsRNA, strongly influences the level of TLR3 activation. Crystalline complexes that present dsRNA at a spacing that matches with the steric size of TLR3 can recruit and engage multiple TLR3 receptors, driving receptor clustering and immune amplification, whereas crystalline complexes that exhibit poor steric matching do not. Reverse-transcription quantitative PCR of IL-6 during siRNA knockdown of TLR3 confirms that cytokine production is due to TLR3: High levels of IL-6 transcription are observed for sterically matched complexes without TLR3 knockdown, whereas such activity is abrogated with TLR3 knockdown.

  22. The Critical and Multifunctional Roles of Antimicrobial Peptides in Dermatology Peer-reviewed

    Toshiya Takahashi, Richard L. Gallo

    DERMATOLOGIC CLINICS　35　(1)　39-+　2017/01

    DOI： 10.1016/j.det.2016.07.006 　

    ISSN： 0733-8635

    eISSN： 1558-0520

  23. Therapeutic drug monitoring of patients with psoriasis during tumour necrosis factor (TNF)-alpha antagonist treatment using a novel interleukin-8 reporter cell line Peer-reviewed

    Y. Kimura, R. Shimada-Omori, T. Takahashi, K. Tsuchiyama, Y. Kusakari, K. Yamasaki, R. Nishikawa, C. Nishigori, S. Aiba

    BRITISH JOURNAL OF DERMATOLOGY　175　(5)　979-987　2016/11

    DOI： 10.1111/bjd.14717 　

    ISSN： 0007-0963

    eISSN： 1365-2133

  24. The Parathyroid Hormone Second Receptor PTH2R and its Ligand Tuberoinfundibular Peptide of 39 Residues TIP39 Regulate Intracellular Calcium and Influence Keratinocyte Differentiation Peer-reviewed

    Emi Sato, Jun Muto, Ling-Juan Zhang, Christopher A. Adase, James A. Sanford, Toshiya Takahashi, Teruaki Nakatsuji, Ted B. Usdin, Richard L. Gallo

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　136　(7)　1449-1459　2016/07

    DOI： 10.1016/j.jid.2016.02.814 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  25. Optimization of the IL-8 Luc assay as an in vitro test for skin sensitization Peer-reviewed

    Yutaka Kimura, Chizu Fujimura, Yumiko Ito, Toshiya Takahashi, Yoshihiro Nakajima, Yoshihiro Ohmiya, Setsuya Aiba

    TOXICOLOGY IN VITRO　29　(7)　1816-1830　2015/10

    DOI： 10.1016/j.tiv.2015.07.006 　

    ISSN： 0887-2333

  26. Successful adalimumab treatment of a psoriasis vulgaris patient with hemodialysis for renal failure: A case report and a review of the previous reports on biologic treatments for psoriasis patients with hemodialysis for renal failure Peer-reviewed

    Yoshiyuki Kusakari, Kenshi Yamasaki, Toshiya Takahashi, Kenichiro Tsuchiyama, Ryoko Shimada-Omori, Mei Nasu-Tamabuchi, Setsuya Aiba

    JOURNAL OF DERMATOLOGY　42　(7)　727-730　2015/07

    DOI： 10.1111/1346-8138.12901 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  27. BRAF V600E遺伝子変異を認めたmulti-spotted malignant melanoma in situの1例

    岩間 英明, 藤村 卓, 高橋 隼也, 古舘 禎騎, 神林 由美, 柿崎 彩, 草刈 良之, 芳賀 貴裕, 橋本 彰, 相場 節也

    日本皮膚科学会雑誌　125　(4)　941-941　2015/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  28. Isolated collagenoma developing on the scalp Peer-reviewed

    Toshiya Takahashi, Taku Fujimura, Yumi Kambayashi, Yukikazu Numata, Setsuya Aiba

    EUROPEAN JOURNAL OF DERMATOLOGY　24　(6)　704-706　2014/12

    DOI： 10.1684/ejd.2014.2445 　

    ISSN： 1167-1122

    eISSN： 1952-4013

  29. Evaluation of the Multi-ImmunoTox Assay composed of 3 human cytokine reporter cells by examining immunological effects of drugs Peer-reviewed

    Yutaka Kimura, Chizu Fujimura, Yumiko Ito, Toshiya Takahashi, Setsuya Aiba

    TOXICOLOGY IN VITRO　28　(5)　759-768　2014/08

    DOI： 10.1016/j.tiv.2014.02.013 　

    ISSN： 0887-2333

  30. 外陰部有棘細胞癌にneoadjuvant chemotherpyが著効し、寛解を得た一例

    志藤 光介, 沼田 透効, 石原 志乃, 玉渕 恵里佳, 高橋 隼也, 藤村 卓, 芳賀 貴裕, 橋本 彰, 山崎 研志, 相場 節也

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集　30回　148-148　2014/07

    Publisher: (一社)日本皮膚悪性腫瘍学会

  31. 骨髄移植前後に生じたFusarium solani感染による結節性紅斑様皮疹の一例

    高橋 隼也, 山崎 研志, 森谷 邦彦, 安澤 数史, 望月 隆, 相場 節也

    日本皮膚科学会雑誌　124　(4)　839-839　2014/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  32. In vivo imaging demonstrates ATP release from murine keratinocytes and its involvement in cutaneous inflammation after tape stripping Peer-reviewed

    Toshiya Takahashi, Yutaka Kimura, Kazuki Niwa, Yoshihiro Ohmiya, Taku Fujimura, Kenshi Yamasaki, Setsuya Aiba

    Journal of Investigative Dermatology　133　(10)　2407-2415　2013

    Publisher: Nature Publishing Group

    DOI： 10.1038/jid.2013.163 　

    ISSN： 1523-1747 0022-202X

  33. The in vivo imaging of extracellular ATP reveals that ATP released from viable keratinocytes initiates inflammation in skin barrier disruption

    T. Takahashi, Y. Kimura, Y. Nakajima, Y. Ohmiya, K. Yamasaki, S. Aiba

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　132　S16-S16　2012/09

    ISSN： 0022-202X

  34. An In Vitro Test to Screen Skin Sensitizers Using a Stable THP-1-Derived IL-8 Reporter Cell Line, THP-G8 Peer-reviewed

    Toshiya Takahashi, Yutaka Kimura, Rumiko Saito, Yoshihiro Nakajima, Yoshihiro Ohmiya, Kenshi Yamasaki, Setsuya Aiba

    TOXICOLOGICAL SCIENCES　124　(2)　359-369　2011/12

    DOI： 10.1093/toxsci/kfr237 　

    ISSN： 1096-6080

  35. Major royal jelly protein 3 as a possible allergen in royal jelly-induced anaphylaxis Peer-reviewed

    Yoko Mizutani, Yoshinao Shibuya, Toshiya Takahashi, Takahiko Tsunoda, Tatsuya Moriyama, Mariko Seishima

    JOURNAL OF DERMATOLOGY　38　(11)　1079-1081　2011/11

    DOI： 10.1111/j.1346-8138.2010.01179.x 　

    ISSN： 0385-2407

  36. An in vitro Test to Screen Skin Sensitizers Using a Stable THP-1-derived IL-8 Reporter Cell Line, THP-G8

    Toshiya Takahashi, Yutaka Kimura, Rumiko Saito, Yoshihiro Nakajima, Yoshihiro Ohmiya, Kenshi Yamasaki, Setsuya Aiba

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　S91-S91　2011/09

    ISSN： 0022-202X

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Misc. 11

  1. 乳児の皮下に多発した神経芽腫の1例

    秋野 萌子, 高橋 隼也, 小林 愛里, 大熊 崇生, 古舘 禎騎, 土山 健一郎, 橋本 彰, 相場 節也, 森谷 邦彦, 笹原 洋二

    日本皮膚科学会雑誌　131　(9)　2075-2075　2021/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  2. A retrospective study evaluating the outcomes of high-dose methylprednisolone pulse therapy for 483 patients with moderate-to-severe alopecia areata

    M. Wada-Irimada, M. Mizuashi, T. Takahashi, G. Tojo, K. Onami, K. Shido, E. Otake, S. Yusa, K. Tanita, E. Yamazaki, S. Aiba, K. Yamasaki

    British Journal of Dermatology　2021

    Publisher: John Wiley and Sons Inc

    DOI： 10.1111/bjd.20644 　

    ISSN： 1365-2133 0007-0963

  3. 【新時代を迎えたアトピー性皮膚炎】悪化因子対策が症状改善に必要であった,デュピルマブの使用症例

    小澤 麻紀, 高橋 隼也, 相場 節也

    皮膚病診療　42　(10)　870-873　2020/10

    Publisher: (株)協和企画

    ISSN： 0387-7531

  4. 自験例を含めた特発性後天性全身性無汗症に対するステロイドパルス療法の有効性についての検討

    吉田 紗彩, 高橋 隼也, 瀬川 雄一朗, 大竹 映香, 遠野 久幸, 神林 由美, 土山 健一郎, 浅野 雅之, 水芦 政人, 相場 節也

    日本皮膚科学会雑誌　129　(5)　1223-1223　2019/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  5. Isolated collagenomaの1例とその免疫組織学的所見

    高橋 隼也, 藤村 卓, 神林 由美, 沼田 透効, 相場 節也

    日本皮膚科学会雑誌　125　(4)　928-928　2015/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  6. Anti-TNF-alpha neutralizing activity of patients' sera evaluated with a novel interleukin (il)-8 reporter cell line correlates with the clinical response to anti-TNF-alpha antibody

    Y. Kimura, R. S. Omori, T. Takahashi, K. Tsuchiyama, Y. Kusakari, K. Yamasaki, S. Aiba

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY　27　19-19　2013/07

    ISSN： 0926-9959

    eISSN： 1468-3083

  7. Status of autophagy and mTOR associate with mortality and cell survival of angiosarcoma

    T. Takahashi, K. Yamasaki, S. Aiba

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　133　S61-S61　2013/05

    ISSN： 0022-202X

  8. A novel interleukin (IL)-8 reporter cell line, THP-G8, can evaluate anti-tumor necrosis factor (TNF)-alpha neutralizing activity of patients' sera and predict drug effectiveness during anti-TNF-alpha antibody therapy

    Y. Kimura, R. S. Omori, T. Takahashi, K. Tsuchiyama, Y. Kusakari, K. Yamasaki, S. Aiba

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　133　S161-S161　2013/05

    ISSN： 0022-202X

  9. Allergic Contact Dermatitis and Small Vessel Vasculitis as a Manifestation of Occupational Exposure

    Yutaka Kimura, Toshiya Takahashi, Shigeaki Nishii, Yoshihiro Ohmiya, Setsuya Aiba

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　S74-S74　2011/09

    ISSN： 0022-202X

  10. The molecular analysis of IL-8 production by hapten-stimulated monocytes using a stable THP-1-derived IL-8 reporter cell line

    Yutaka Kimura, Toshiya Takahashi, Shigeaki Nishii, Yoshihiro Ohmiya, Setsuya Aiba

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　S74-S74　2011/09

    ISSN： 0022-202X

  11. Two Cases of Immediate Hypersensitivity to Royal Jelly Examined by Immunoblotting with Their Sera

    TAKAHASHI Toshiya, OKUNO Kousei, TSUNODA Takahiko, MORIYAMA Tatsuya

    Japanese journal of dermatology　118　(1)　43-46　2008/01/20

    Publisher: 日本皮膚科学会

    DOI： 10.14924/dermatol.118.43 　

    ISSN： 0021-499X

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Research Projects 8

  1. Exploring novel skincare treatments for atopic dermatitis using artificial antimicrobial peptides.

    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: Tohoku University

    2025/04/01 - 2028/03/31

  2. The mechanism how cathelicidin causes inflammation in dermatomyositis

    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: Tohoku University

    2022/04/01 - 2025/03/31

  3. Antimicrobial peptide, Cathelicidin in psoriasis, infectious disease, and metabolic syndrome

    Takahashi Toshiya

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Tohoku University

    2020/04/01 - 2022/03/31

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    In cultured human keratinocytes, the addition of representative damage-associated molecular patterns (DAMPs), together with the antimicrobial peptide LL-37, induced proinflammatory cytokines that are important in the pathogenesis of psoriasis. These inductions were inhibited by scavenger receptor (SR) inhibition. This indicates that LL-37 binds to these DAMPs and is taken up by the SR into the cells followed by inducing inflammation. Immunostaining of tissue specimens from psoriasis patients showed that IL-36γ was observed in the epidermis only in cases with LL-37-positive cells in the dermis, implying that LL-37 may stimulate IL-36γ production from epidermal keratinocytes in vivo.

  4. Function of Antimicrobial Peptide Cathelicidin in Psoriasis, Infections, and Metabolic Syndrome

    Takahashi Toshiya

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tohoku University

    2019/04/01 - 2020/03/31

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    We added poly(dA:dT) (mock dsDNA) and high mobility group box 1 protein (HMGB1), which are representative damage-associated molecular patterns (DAMPs) and known ligands of scavenger receptors, to human cultured keratinocytes (NHEKs) with or without active form of cathelicidin (LL-37). As a result，inflammatory cytokines such as IL-6 and TNF-α were more strongly induced than those LL-37 or DAMPs alone. In addition, immunohistochemistry using lesional skin from psoriasis patients revealed that IL-36γ was positive in the epidermis only in cases with a large number of LL-37-positive keratinocytes. These results suggest that LL-37 and its associated inflammation induce IL-36γ, which is important for the pathogenesis of psoriasis.

  5. 表皮機能形成過程におけるオートファジーによる小器官リサイクル機構

    高橋 隼也

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 若手研究(B)

    Institution: 東北大学

    2015/04/01 - 2017/03/31

  6. 血管肉腫における哺乳類ラパマイシン標的蛋白質経路とオートファジー機構の病態関与

    沼田 透効, 高橋 隼也, 山崎 研志

    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: 東北大学

    2014/04/01 - 2015/03/31

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    血管肉腫組織におけるmTOR経路とオートファジー機構関連分子の発現確認を免疫組織学的に検討した。mTOR経路関連分子では、血管肉腫において、mTORの発現増強を確認し、PI3K, AKT, TSC1, TSC2の発現が血管肉腫組織内に確認された。オートファジー経路関連分子では、ATG14とATG8 (LC3-I/LC3-III)の発現が増強している血管肉腫組織を確認した。発現は組織辺縁に強く、組織中央部においてはATG8 (LC3-I/LC3-III)の発現は乏しかった。これらの結果は、細胞増殖・分裂が多く起こっている腫瘍辺縁の領域においてオートファジー径路が働いている可能性を示唆した。 血管内皮細胞を用いたmTOR経路とオートファジー機構関連分子の強発現・抑制による細胞動向の検討を行った。オートファジー経路の抑制化合物を添加した後に細胞増殖をMTT法にて検討したところ、血管内皮細胞の細胞死の比率が高くなったことが確認された。すなわち、オートファジー径路は血管内皮細胞の増殖維持に正に働き、その抑制は細胞死を誘導することを示唆した。また、オートファジー経路の抑制化合物を添加した条件下では、mTOR経路関連分子とオートファジー機構関連分子の遺伝子発現が誘導されていた。以上のことから血管系細胞では、mTOR経路関連分子とオートファジー機構関連分子が、腫瘍組織・細胞の増殖に関連しており、mTOR経路関連分子とオートファジー機構関連分子のフィードバック機構の存在が想起された。

  7. Organella recycle system by autophagy in epidermis

    TAKAHASHI Toshiya

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tohoku University

    2013/08/30 - 2015/03/31

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    We confirmed the expression of LC3B, which is key molecule in autophagy, to epidermis and skin adnexa. In addition, in psoriasis and atopic dermatitis, expression of LC3B in the epidermis granular layer was more strongly seen. Moreover, by the experiment using the normal human epidermal keratinocyte, TLR9 ligand stimulation enhanced expression of LC3B. These results suggested association between autophagy and synthesis of many molecules, and that bacterial infection may induce autophagy and following various material composition in the skin, but did not come to clarify the mechanism.

  8. The importance of mTOR pathway and autophagy mechanism in angiosarcoma survival

    NUMATA Yukikazu, TAKAHASHI Toshiya, YAMASAKI Kenshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2012/04/01 - 2014/03/31

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    The purpose of this study is to check the molecular condition of a patient mechanism of angiosarcoma which has poor prognosis. Especially, I expect mTOR course and participation of the automatic fuzzy mechanism in that with a main purpose. After, in 2012, examining the expression of related molecules with the angiosarcoma tissue for immunohistology; in comparison with a normalcy blood vessel wall strong; confirmed that developed, and what was activated constantly particularly an automatic fuzzy system course was suggested. After using a repressor and the automatic fuzzy repressor of the mTOR course in the culture system of the angiosarcoma cell, I confirmed the apoptotic instruction of the neoplastic cell. I confirmed the expression of both courses with the normal skin in 2013. As for these results, the inhibition of both courses suggested the possibility of new treatment of angiosarcoma.

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