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Generation of bullous pemphigoid antigen specific T cell clones

Research Project

Project/Area Number 17H04238
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionHokkaido University

Principal Investigator

UJIIE Hideyuki  北海道大学, 大学病院, 講師 (60374435)

Co-Investigator(Kenkyū-buntansha) 岩田 浩明  北海道大学, 大学病院, 助教 (20397334)
西江 渉  北海道大学, 医学研究院, 准教授 (20443955)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
KeywordsT細胞株 / 水疱性類天疱瘡 / 17型コラーゲン / BP180 / アクティブマウスモデル / T細胞受容体 / サイトカイン / 自己免疫性水疱症 / 皮膚炎 / トランスジェニックマウス
Outline of Final Research Achievements

Bullous pemphigoid (BP) is a most common autoimmune blistering disorder, which preferentially affects elderly people. It is caused by autoantibodies to type XVII collagen (COL17, BP180) at the dermal-epidermal junction of the skin. Although autoreactive T cells is important to produce autoantibody, the pathogenicity of COL17-reactive T cells is still largely unclear. In this study, we have successfully established human COL17-reactive T cell lines by stimulating and culturing lymphocytes obtained from human COL17-immunized mice. Those T cell lines are CD4+ effector T cells which produce IFN-gamma and showed weak pathogenicity in a mouse model.

Academic Significance and Societal Importance of the Research Achievements

本研究で樹立したヒトCOL17反応性T細胞株を解析することで、水疱性類天疱瘡(BP)における自己反応性T細胞の病態機序が明らかとなる。また、COL17は表皮と真皮の境界部に存在するため、扁平苔癬や移植片対宿主病(GVHD)といった疾患の病態解明の手掛かりとなる可能性が高い。さらにCOL17は毛包に発現し重要な役割を果たしていることから、毛包性疾患の病態解明に繋がる可能性もある。また、本研究で確立したT細胞株樹立の手法は他の様々な自己抗原に対するT細胞株の樹立にも応用可能であり、多くの自己免疫疾患の病態解明に寄与し得るものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (9 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Prevalence of infectious diseases in patients with autoimmune blistering diseases2020

    • Author(s)
      Ujiie Inkin、Ujiie Hideyuki、Yoshimoto Norihiro、Iwata Hiroaki、Shimizu Hiroshi
    • Journal Title

      The Journal of Dermatology

      Volume: 47 Issue: 4 Pages: 378-384

    • DOI

      10.1111/1346-8138.15244

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and immunological features of pemphigus relapse2019

    • Author(s)
      Ujiie I.、Ujiie H.、Iwata H.、Shimizu H.
    • Journal Title

      British Journal of Dermatology

      Volume: 180 Issue: 6 Pages: 1498-1505

    • DOI

      10.1111/bjd.17591

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immune Reaction to Type XVII Collagen Induces Intramolecular and Intermolecular Epitope Spreading in Experimental Bullous Pemphigoid Models2019

    • Author(s)
      Ujiie Hideyuki、Yoshimoto Norihiro、Natsuga Ken、Muramatsu Ken、Iwata Hiroaki、Nishie Wataru、Shimizu Hiroshi
    • Journal Title

      Frontiers in Immunology

      Volume: 10 Pages: 1-10

    • DOI

      10.3389/fimmu.2019.01410

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Case of autoimmune intraepidermal and subepidermal blistering disease in which autoantibodies to desmoglein 1 and BP230 coexist2019

    • Author(s)
      Sugai Tatsuro、Ujiie Hideyuki、Nakamura Hiroyuki、Kikuchi Kazuhiro、Iwata Hiroaki、Shimizu Hiroshi
    • Journal Title

      The Journal of Dermatology

      Volume: 印刷中 Issue: 6

    • DOI

      10.1111/1346-8138.14734

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characteristics of IgG subclasses and complement deposition in BP230-type bullous pemphigoid2018

    • Author(s)
      Zheng M.、Ujiie H.、Iwata H.、Muramatsu K.、Yoshimoto N.、Ito T.、Ujiie I.、Shimizu S.、Sato-Matsumura K.C.、Shimizu H.
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: 33 Issue: 3 Pages: 595-600

    • DOI

      10.1111/jdv.15325

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bullous pemphigoid with the deposition of IgG2 but not IgG1, IgG3 nor IgG4 autoantibodies at the basement membrane zone2018

    • Author(s)
      Yoshimoto N.、Ujiie H.、Zheng M.、Iwata H.、Kosumi H.、Hata H.、Shimizu H.
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: 32 Issue: 9

    • DOI

      10.1111/jdv.14920

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] New insights into bullous pemphigoid.2019

    • Author(s)
      Ujiie H
    • Organizer
      The 24th World Congress of Dermatology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanism of autoantibody production in bullous pemphigoid2019

    • Author(s)
      Ujiie H
    • Organizer
      Japan-Singapore International Skin Conference 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Clarification of the mechanism of the breakdown of self-tolerance in bullous pemphigoid2019

    • Author(s)
      Ujiie H
    • Organizer
      The 44th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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