TAKAHASHI Hayato

写真a

Affiliation

School of Medicine, Department of Dermatology （Shinanomachi）

Position

Associate Professor
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Academic Background 【 Display / hide 】

  • 1994.04
    -
    2000.03

    慶應義塾大学, 医学部

    University, Graduated

  • 2002.04
    -
    2006.03

    慶應義塾大学大学院, 医学研究科, 内科系皮膚科学

    Graduate School, Withdrawal after completion of doctoral course requirements, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, 慶應義塾大学, Coursework, 2009.01

    Novel system evaluating in vivo pathogenicity of desmoglein 3-reactive T cell clones using murine pemphigus vulgaris.

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Licenses and Qualifications 【 Display / hide 】

  • 医師免許, 2000.04

  • 日本皮膚科学会認定皮膚科専門医, 2007.10

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Research Areas 【 Display / hide 】

  • Life Science / Dermatology

  • Life Science / Immunology

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Research Keywords 【 Display / hide 】

  • Desmoglein

  • Pemphigus

  • Interface dermatitis

  • Drug eruption

  • Food allergy

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Books 【 Display / hide 】

  • 眼疾患アトラスシリーズ　第3巻『外眼部アトラス』

    高橋勇人, 総合医学社, 2019.10

    Scope: 丹毒,  Contact page： 108-109

  • 皮膚科のくすりの使い方

    高橋勇人, じほう, 2019.08

    Scope: 薬疹,  Contact page： 141-144

  • 私の治療2019-20年度

    高橋勇人, 日本医事新報社, 2019.07

    Scope: 天疱瘡,  Contact page： 877-878

  • ガイドライン外来診療 2019

    高橋勇人, 日経メディカル開発, 2019.03

    Scope: 薬疹,  Contact page： 329-334

  • 皮膚症状110症例でみる内科疾患

    高橋勇人, 日本医事新報社, 2018.09

    Scope: 悪性リンパ腫③　腫瘍随伴性天疱瘡,  Contact page： 22-23

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Papers 【 Display / hide 】

  • Attenuation of OX40 signaling suppression by age disrupts peripheral deletion of CD4<sup>+</sup> T cells specific for the epidermal autoantigen desmoglein 3

    Iriki H., Mukai M., Asahina Y., Kubo Y., Ito H., Amagai M., Takahashi H.

    Immunity and Ageing （Immunity and Ageing)  20 （ 1 ） 26 2023.12

    Accepted,  ISSN  1742-4933

    　View Summary

    Various autoimmune responses increase with age, but the underlying mechanism is not clear. In this study, we used CD4+ T cells expressing a transgenic T cell receptor specific for desmoglein 3 (Dsg3), which is the target antigen of the autoimmune bullous disease pemphigus vulgaris, to examine how peripheral immunological tolerance against pathogenic autoreactive CD4+ T cells changes with age. Dsg3-specific T cells were deleted within 14 days after adoptive transfer into young mice (8 weeks old), while they escaped deletion when transferred into older mice over 42 weeks old. Dsg3-specific T cells produced higher levels of the proinflammatory cytokine IFN-γ in aged mice than in young mice. In addition, the expression levels of both OX40 and Birc5, which are important for cell survival in T cell clonal proliferation, were higher in aged than in young mice. The dysfunction in suppressing proinflammatory cytokine secretion and Birc5 upregulation in Dsg3-specific autoreactive T cells may reflect an aspect of the preliminary steps in autoimmune disease development in the aged population. Understanding this mechanism may lead to better risk evaluation of autoimmune disease development and to onset prevention.

  • Diverse Role of OX40 on T Cells as a Therapeutic Target for Skin Diseases

    Iriki H., Takahashi H., Amagai M.

    Journal of Investigative Dermatology （Journal of Investigative Dermatology)  143 （ 4 ） 545 - 553 2023.04

    ISSN  0022202X

    　View Summary

    OX40 is an important costimulatory molecule for T-cell expansion and survival. Because OX40 is expressed on most T-cell subsets, it is an attractive therapeutic target for a variety of T-cell‒mediated diseases. Clinical trials are already underway for some skin inflammatory diseases. In this review, we present various observations that improve our understanding of how OX40-targeted therapy can be applied for skin inflammatory diseases, such as atopic dermatitis and psoriasis, T helper (Th)2- and Th17-mediated diseases, respectively. The important OX40/OX40L-mediated interaction between T cells and other immune cells is also discussed in terms of skin autoimmune diseases, such as alopecia areata and pemphigus. Regulatory T cells (Tregs) highly express OX40, and the skin harbors a large Treg population; thus, understanding how OX40-targeted treatment acts on Tregs is vital for the development of therapeutic strategies for various skin diseases.

  • T cell autoimmunity and immune regulation to desmoglein 3, a pemphigus autoantigen

    Takahashi H., Iriki H., Asahina Y.

    Journal of Dermatology （Journal of Dermatology)  50 （ 2 ） 112 - 123 2023.02

    ISSN  03852407

    　View Summary

    Pemphigus is a life-threatening autoimmune bullous disease mediated by anti-desmoglein IgG autoantibodies. Pemphigus is mainly classified into three subtypes: pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. The pathogenicity of autoantibodies has been extensively studied. Anti-human CD20 antibody therapy targeting B cells emerged as a more effective treatment option compared to conventional therapy for patients with an intractable disease. On the other hand, autoreactive T cells are considered to be involved in the pathogenesis based on the test results of human leukocyte antigen association, autoreactive T cell detection, and cytokine profile analysis. Research on the role of T cells in pemphigus has continued to progress, including that on T follicular helper cells, which initiate molecular mechanisms involved in antibody production in B cells. Autoreactive T cell research in mice has highlighted the crucial roles of cellular autoimmunity and improved the understanding of its pathogenesis, especially in paraneoplastic pemphigus. The mouse research has helped elucidate novel regulatory mechanisms of autoreactive T cells, such as thymic tolerance to desmoglein 3 and the essential roles of regulatory T cells, Langerhans cells, and other molecules in peripheral tissues. This review focuses on the immunological aspects of autoreactive T cells in pemphigus by providing detailed information on various related topics.

  • Rituximab therapy for intractable pemphigus: A multicenter, open-label, single-arm, prospective study of 20 Japanese patients

    Yamagami J., Kurihara Y., Funakoshi T., Saito Y., Tanaka R., Takahashi H., Ujiie H., Iwata H., Hirai Y., Iwatsuki K., Ishii N., Sakurai J., Abe T., Takemura R., Mashino N., Abe M., Amagai M.

    Journal of Dermatology （Journal of Dermatology)  50 （ 2 ） 175 - 182 2023.02

    ISSN  03852407

    　View Summary

    This was a multicenter clinical trial of rituximab, a chimeric monoclonal IgG antibody directed against CD20, for the treatment of refractory pemphigus vulgaris and pemphigus foliaceus. In total, 20 patients were treated with two doses of rituximab (1000 mg; 2 weeks apart) on days 0 and 14. The primary end point was the proportion of patients who achieved complete or partial remission on day 168 following the first rituximab dose. Of the 20 enrolled patients, 11 (55%) and four (20%) achieved complete and partial remission, respectively; therefore, remission was achieved in a total of 15 patients (75.0% [95% confidence interval, 50.9%–91.3%]). It was demonstrated that the remission rate was greater than the prespecified threshold (5%). In addition, a significant improvement in clinical score (Pemphigus Disease Area Index) and decrease in serum anti-desmoglein antibody level were observed over time. Four serious adverse events (heart failure, pneumonia, radial fracture, and osteonecrosis) were recorded in two patients, of which only pneumonia was considered causally related with rituximab. The level of peripheral blood CD19-positive B lymphocytes was decreased on day 28 after rituximab treatment and remained low throughout the study period until day 168. Our results confirm the efficacy and safety of rituximab therapy for refractory pemphigus in Japanese patients.

  • Meeting Report: ISID2023 Tokyo Satellite Meeting. International Symposium on Autoimmunity Targeting the Skin. -Pemphigus, Pemphigoid, and Beyond-

    Yamagami J., Takahashi H., Amagai M.

    Journal of Dermatological Science （Journal of Dermatological Science)   2023

    Accepted,  ISSN  09231811

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • IL-27 is crucial in anti-desmoglein 3 autoantibody production in pemphigus vulgaris mouse model

    Kamata A, Takahashi H, Yoshida H, Yamagami J, Amagai M

    48th Annual Meeting of the Japanese Society for Immunology (Hamamatsu, Japan) , 

    2019.12

  • Blockade of pathogenic immunoglobulin class-switch is a tolerogenic process to prevent pemphigus development in desmoglein 3-sepecific B cell receptor knock-in mouse

    Nomura H, Takahashi H, Yamagami J, Fujii H, Koseki H, Watanabe T, Ohara O, Koyasu S, Amagai M

    48th Annual Meeting of The Japanese Society for Immunology (Hamamatsu, Japan) , 

    2019.12

  • The clinical utility of basophil activation test in diagnosis of hypersensitivity due to fermented soybeans,natto

    Fukuda R, Ouchi T, Shiiya C, Yasuda-Sekiguchi F, Kouno M, Takahashi S, Amagai M, Takahashi H

    EAACI Allegy School on Food Allergy (Paris, France) , 

    2019.12

  • 薬疹　経過中に自己抗体が出現した薬剤性過敏症症候群および疑い例の検討

    椎谷千尋, 大内健嗣, 舩越建, 天谷雅行, 高橋勇人

    第49回日本皮膚免疫アレルギー学会総会学術大会 (横浜) , 

    2019.11

  • Single-cell RNA-seq reveals the transcriptional landscape and heterogeneity of autoreactive B cells in pemphigus patients

    Egami S, Watanabe T, Nomura H, Takahashi H, Yamagami J, Ohara O, Amagai M

    44th Annual meeting of the Japanese Society for Investigative Dermatology (Aomori, Japan) , 

    2019.11

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • ［基盤研究A］ 病態に直結するT細胞レパトアの制御を目指した、新たな免疫制御機構の同定と解析

    2019.04
    -
    2023.03

    基盤研究A, Research grant, Principal investigator

  • ［慶應義塾・学事振興資金（個人研究 特B）］天疱瘡自己抗原に対する末梢性免疫寛容機構の解明

    2018.04
    -
    2019.03

    慶應義塾学事振興資金, No Setting

  • ［革新的先端研究開発支援事業］ PRIME 新規T細胞サブセットを規定するコレルテロール代謝酵素の機能解析と疾患制御への応用

    2016
    -
    2019

    AMED（国立研究開発法人日本医療研究開発機構）-PRIME, No Setting

  • [免疫アレルギー疾患等実用化研究事業 免疫アレルギー疾患実用化研究分野] 重症薬疹サンプルの選定、採取およびウィルス叢と疾患発症との関連性解析

    2015
    -
    Present

    AMED（国立研究開発法人日本医療研究開発機構）, Coinvestigator(s)

  • Molecular mechanism of skin inflammation induced by desmoglein 3-specific T cells

    2014.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

    　View Summary

    Interface dermatitis is a pathological feature which is commonly observed in a variety of skin diseases including lichen plans, severe drug adverse reaction, graft-versus-host disease, paraneoplastic pemphigus and so on. The molecular mechanism that leads to interface dermatitis has not been understood. In this project, we took advantage of genetically engineered mice and discovered that T-bet and Stat1, crucial transcriptional factors in T cell differentiation, are keys in development of interface dermatitis. On the other hand, we also sought to establish a novel concept in the field of Immunology in this project. Through investigating genes which are specifically induced by interleukin (IL)-27, we found that cholesterol metabolizing enzyme is induced by IL-27 and the function contributes to immune regulation. Our results are promisingly expected to be useful to invent a new treatment for skin inflammatory diseases in the future.

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Works 【 Display / hide 】

  • International League of Dermatological Societies-Newsletter「ILDS 2015 Young Dermatologist International Achievement Award(YDIAA) Winners」

    Hayato Takahashi

    2015.12
    , 

    Other

  • 慶應義塾医学部新聞「デスモグレイン3反応性T細胞による新規自己免疫性皮膚炎モデルの確立」

    高橋勇人

    2012.11
    , 

    Other

  • 慶應義塾医学部新聞「日本皮膚科学会　皆見省吾記念賞受賞」

    高橋勇人

    2012.07
    , 

    Other

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Intellectual Property Rights, etc. 【 Display / hide 】

  • 自己免疫疾患における自己抗体産生を抑制するシグナル阻害自己免疫疾患治療剤

    Date applied： 特願2019-214253  2019.11 

    Joint

  • ２５−ヒドロキシコレステロールを有効成分として含有してなる、活性化されたT細胞及び／又はB細胞に選択的な細胞死誘導剤又は細胞死促進剤

    Date applied： 特許出願2016-111556  2016.06 

    Patent, Joint

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Awards 【 Display / hide 】

  • JSID Award

    2022.12, Japanese Society for Investigative Deramtology

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • Young Dermatologist International Achievement Award 2015

    2015.06, International League of Dermatological Societies

  • 三四会奨励賞受賞

    2012.11

    　View Description

    第92回慶應医学会総会(於新棟11階大会議室）にて

  • 平成24年度皆見省吾記念賞

    2012.06

    　View Description

    第111回日本皮膚科学会総会（於京都）にて

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, DERMATOLOGY

    2024

  • LECTURE SERIES, DERMATOLOGY

    2023

  • LECTURE SERIES, DERMATOLOGY

    2022

  • LECTURE SERIES, DERMATOLOGY

    2021

  • LECTURE SERIES, DERMATOLOGY

    2020

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Courses Previously Taught 【 Display / hide 】

  • 皮膚科学

    学校法人慶應義塾大学

    2018.04
    -
    2019.03

  • 皮膚科学講義「皮膚の免疫・アレルギー・薬疹」2017/12/01

    Keio University

    2017.04
    -
    2018.03

  • 皮膚科学講義「アレルギー性皮膚疾患・薬疹」2016/11/24

    Keio University

    2016.04
    -
    2017.03

  • 皮膚科学講義「アレルギー性皮膚疾患・　薬疹」2015/11/24

    Keio University

    2015.04
    -
    2016.03

  • 皮膚科学講義「アレルギー性皮膚疾患・　薬疹」2014/11/26

    Keio University

    2014.04
    -
    2015.03

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Memberships in Academic Societies 【 Display / hide 】

  • 日本炎症再生医学会, 

    2017
    -
    Present

  • 日本免疫学会, 

    2012
    -
    Present

  • 日本研究皮膚科学会, 

    2005
    -
    Present

  • 日本皮膚科学会, 

    2000
    -
    Present
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Committee Experiences 【 Display / hide 】

  • 2017
    -
    Present

    日本研究皮膚科学会　ISID開設準備委員会　委員

  • 2017
    -
    2020

    日本研究皮膚科学会　推薦員会　委員

  • 2014
    -
    2017

    日本研究皮膚科学会　若手セミナー委員会　委員

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