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Clarification of peripheral tolerance mechanism involved in the onset of autoimmune skin diseases

Research Project

Project/Area Number 26253065
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

Amagai Masayuki  慶應義塾大学, 医学部(信濃町), 教授 (90212563)

Co-Investigator(Kenkyū-buntansha) 高橋 勇人  慶應義塾大学, 医学部, 講師 (40398615)
山上 淳  慶應義塾大学, 医学部, 講師 (80327618)
Co-Investigator(Renkei-kenkyūsha) TAKAHASHI Hayato  慶應義塾大学, 医学部, 専任講師 (40398615)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥41,470,000 (Direct Cost: ¥31,900,000、Indirect Cost: ¥9,570,000)
Fiscal Year 2016: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2015: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2014: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Keywords自己免疫 / 免疫寛容 / 天疱瘡 / マウスモデル / デスモグレイン
Outline of Final Research Achievements

Utilizing desmoglein3 (Dsg3)-specific T cells (H1 T cells), two experimental models were established for clarification and analysis of peripheral immune tolerance mechanism. In the first model, we made mice, which lack Dsg3 only in the thymus by applying thymus transplantation into Nude mice, and then performed bone marrow transplantation to these mice from H1-tg mice. In these mice, H1 T cells matured in Dsg3 deficient thymus, and then, disappeared in Dsg3 expressing periphery. In the other model, H1 T cells existing in the periphery of H1-Dsg3-/- mice were adoptively transferred into WT mice. In these WT mice, H1 T cells disappeared after proliferation. Taking advantage of these models, we clarified that peripheral immune tolerance mechanism is initiated by antigen presentation to H1 T cells in skin-draining lymph node, and divided into proliferation phase and disappearance phase, orchestrated by some kinds of cell populations.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (24 results)

All 2017 2016 2015 2014

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (12 results) (of which Int'l Joint Research: 7 results,  Invited: 5 results) Book (2 results)

  • [Journal Article] Pemphigus2017

    • Author(s)
      Kasperkiewicz M, Ellebrecht CT, Takahashi H, Yamagami J, Zillikens D, Payne AS, Amagai M
    • Journal Title

      Nature Reviews Disease Primers

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evaluation of pharyngo-oesophageal involvement in pemphigus vulgaris and its correlation with disease activity2017

    • Author(s)
      Okamura A, Nakamura R, Yamagami J, Ishii K, Kawakubo H, Omori T, Takeuchi H, Amagai M, Kitagawa Y.
    • Journal Title

      Br J Dermatol

      Volume: 176 Issue: 1 Pages: 224-226

    • DOI

      10.1111/bjd.14725

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Validation of chemiluminescent enzyme immunoassay in detection of autoantibodies in pemphigus and pemphigoid.2017

    • Author(s)
      Fujio Y, Kojima K, Hashiguchi M, Wakui M, Murata M, Amagai M, Yamagami J.
    • Journal Title

      J Dermatol Sci

      Volume: 85 Issue: 3 Pages: 208-215

    • DOI

      10.1016/j.jdermsci.2016.12.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Non-pathogenic pemphigus foliaceus (PF) IgG acts synergistically with a directly pathogenic PF IgG to increase blistering by p38MAPK-dependent desmoglein 1 clustering2017

    • Author(s)
      Yoshida K, Ishii K, Shimizu A, Yokouchi M, Amagai M, Shiraishi K, Shirakata Y, Stanley JR, Ishiko A.
    • Journal Title

      J Dermatol Sci

      Volume: 85 Issue: 3 Pages: 197-207

    • DOI

      10.1016/j.jdermsci.2016.12.010

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 天疱瘡におけるデスモグレイン3特異的T細胞の臓器を越えた病原的役割2016

    • Author(s)
      高橋勇人, 天谷雅行
    • Journal Title

      医学のあゆみ

      Volume: 259 Pages: 159-164

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low pathogenicity of anti-desmoglein 3 immunoglobulin G autoantibodies contributes to the atypical clinical phenotypes in pemphigus2015

    • Author(s)
      Saleh MA, Hashimoto R, Kase Y, Amagai M, Yamagami J
    • Journal Title

      J Dermatol

      Volume: 42 Issue: 7 Pages: 685-689

    • DOI

      10.1111/1346-8138.12888

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma.2015

    • Author(s)
      Adachi T, Kobayashi T, Sugihara E, Yamada T, Ikuta K, Pittaluga S, Saya H, Amagai M, Nagao K.
    • Journal Title

      Nature Med.

      Volume: 21 Issue: 11 Pages: 1272-1279

    • DOI

      10.1038/nm.3962

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] デスモグレイン3特異的T細胞によって誘導される多彩な皮膚病理2015

    • Author(s)
      高橋勇人、天谷雅行
    • Journal Title

      実験医学

      Volume: 33 Pages: 1948-1953

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 皮膚疾患におけるT細胞の重要な役割2014

    • Author(s)
      高橋勇人, 天谷雅行
    • Journal Title

      実験医学

      Volume: 32 Pages: 2854-2860

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 天疱瘡:抗デスモグレイン抗体2014

    • Author(s)
      山上淳, 天谷雅行
    • Journal Title

      分子リウマチ治療

      Volume: 7 Pages: 113-116

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] FcgRllb is critical to establish clonal ignorance and suppress pemphigus phenotype in pathogenic anti-desmoglein 3 antibody knock-in mice2016

    • Author(s)
      Nomura H, Kase Y, Yamagami J, Wada N, Koyasu S, Takahashi H, Amagai M
    • Organizer
      41st Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      仙台国際センター(宮城県仙台市青葉区)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] p38MAPK contributes to loss of cell adhesion through clustering of desmoglein 1 but is not required for blistering in pemphigus foliaceus2016

    • Author(s)
      Yoshida K, Ishii K, Shimizu A, Yokouchi M, Amagai M, Stanley JR, Ishiko A
    • Organizer
      41st Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      仙台国際センター(宮城県仙台市青葉区)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] Novel immune regulation by CD4+ T cells via cholesterol 25-hydroxylase pathway.2016

    • Author(s)
      Takahashi H, Nomura H, Iriki H, Mikami Y, Kanno Y, Kubo A, O'shea J, Amagai M
    • Organizer
      46th Annual Meeting of the European Society for Dermatological Research
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Peripheral tolerance to Dsg3-specific CD4 T cells2016

    • Author(s)
      Amagai M
    • Organizer
      Pathogenesis of Pemphigus and Pemphigoid (PPP) Meeting 2016
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2016-09-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Activities of the research team for rare and intractable skin diseases2015

    • Author(s)
      Amagai M
    • Organizer
      The 40th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      Okayama Convention Center (Okayama City, Okayama Prefecture, Japan)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] stablishment of thymus transplant model to analyze peripheral T cell tolerance against pemphigus autoantigen, desmoglein 32015

    • Author(s)
      Iriki H, Takahashi H, Wada N, Amagai M
    • Organizer
      The 44th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Sapporo Convention Center (Sapporo City, Hokkaido, Japan)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intravenous immunoglobulin regulates anti-desmoglein 3 autoantibody production in B220- antibody-producing cells in mice with pemphigus vulgaris2015

    • Author(s)
      Kase Y, Yamagami J, Wada N, Takahashi H, Koyasu S, Amagai M
    • Organizer
      45th Annual Meeting of the European Society for Dermatological Research
    • Place of Presentation
      Rotterdam (The Netherlands)
    • Year and Date
      2015-09-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Central and peripheral tolerance to Dsg3-specific CD4 T cells in mice2015

    • Author(s)
      Amagai M
    • Organizer
      Pemphigus Meeting
    • Place of Presentation
      Paris (France)
    • Year and Date
      2015-09-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Innovative approaches to immunobullous disease2015

    • Author(s)
      Amagai M
    • Organizer
      95th Annual Meeting of British Association of Dermatologists
    • Place of Presentation
      Manchester (UK)
    • Year and Date
      2015-07-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Skin-infiltrating CD4+ lymphoma cells depend on hair follicle-derived IL-72014

    • Author(s)
      Adachi T, Kobayashi T, Sugihara E, Fukuda K, Ohyama M, Saya H, Yamada T, Amagai M, Nagao K
    • Organizer
      第39回日本研究皮膚科学会学術大会・総会
    • Place of Presentation
      大阪
    • Year and Date
      2014-12-12 – 2014-12-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] Towards antigen-specific immune suppression in pemphigus2014

    • Author(s)
      Amagai M
    • Organizer
      Inflammatory Skin Disease Summit: The Translational Revolution
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2014-11-19 – 2014-11-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Tolerance break by immunoglobulin class switch recombination induces pemphigus vulgaris in mice2014

    • Author(s)
      Wada N, Fujii H, Ishikura T, Koseki H, Amagai M, Koyasu S
    • Organizer
      The 44th Annual Meeting of European Society for Dermatological Research
    • Place of Presentation
      Copenhagen, Denmark
    • Year and Date
      2014-09-10 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Book] 臨床検査データブック2017-20182017

    • Author(s)
      天谷雅行
    • Total Pages
      1049
    • Publisher
      医学書院
    • Related Report
      2016 Annual Research Report
  • [Book] Immunology of the Skin2016

    • Author(s)
      Yamagami J, Takahashi H, Amagai M.
    • Total Pages
      504
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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