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The characterization and role of the novel differential pathway of autoreactive T cells in immunological tolerance.

Research Project

Project/Area Number 26860745
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Collagenous pathology/Allergology
Research InstitutionThe University of Tokyo

Principal Investigator

Akahira Lisa  東京大学, 医学部附属病院, 助教 (70725192)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords自己反応性T細胞 / 免疫学的寛容 / 胸腺 / 自己免疫 / 膠原病
Outline of Final Research Achievements

Clonal deletion and Foxp3+ regulatory T cell lineage commitment are well-known as the fate of autoreactive thymocytes. However, other pathways have not been fully clarified yet. On the other hand, the mechanism of autoantibody production in human disease remains incompletely understood. Here, we show that autoreactive CD4+ T cells can differentiate into naturally occurring autoreactive B cell-helper T (natural TAH) cells, which are rendered anergic in vivo, in the thymus of gene-manipulated and wild-type mice. Natural TAH cells are defined as IL-21-producing Bcl-6+Helios+ Foxp3-PD-1+CD200+CXCR5-CD4+ T cells, and promote B cells to produce immunoglobulin. Although Bcl-6 is required for generation of natural TAH cells, they can be distinguished from traditional follicular helper T cells in self-reactivity, CXCR5 expression, and ontogeny. This new differential pathway into natural TAH cells might be a key regulator of autoimmune disease with autoantibodies.

Report

(3 results)
  • 2017 Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (4 results)

All 2015 2014

All Presentation (4 results)

  • [Presentation] Reciprocal roles of intestinal microbiota in the pathogenesis of organ-specific autoimmune diseases in a lymphopenia-induced autoimmunity mouse model2015

    • Author(s)
      Eri Toshiki, Kawahata Kimito, Bannai Ei, Kanzaki Takeyuki, Akahira Risa, Michishita Kazuya, Yamamoto Kazuhiko
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] シトルリン化抗原特異的B細胞の標的療法はコラーゲン誘発性関節炎を軽減する(Targeting therapy of citrullinated antigen-specific B cells attenuates collagen-induced arthritis)2014

    • Author(s)
      Michishita Kazuya, Kawahata Kimito, Kanzaki Takeyuki, Akahira Lisa, Eri Toshiki, Yamamoto Kazuhiko
    • Organizer
      第58回 日本リウマチ学会
    • Place of Presentation
      東京・グランドプリンスホテル新高輪
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] PM/DM、SS、IgG4-RD リンパ球減少誘発性自己免疫における抗核抗体産生において腸細菌叢は重要な役割を果たす(PM/DM, SS, IgG4-RD Intestinal microbiota plays a critical role in the production of antinuclear antibodies in lymphopenia-induced autoimmunity)2014

    • Author(s)
      Eri Toshiki, Kawahata Kimito, Imamura Mitsuru, Kanzaki Takeyuki, Akahira Lisa, Michishita Kazuya, Yamamoto Kazuhiko
    • Organizer
      第58回 日本リウマチ学会
    • Place of Presentation
      東京・グランドプリンスホテル新高輪
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 自己抗体 リンパ球減少誘発性自己免疫での抗核抗体の産生において腸細菌叢は重要な役割を果たす(Intestinal microbiota plays a critical role in the production of antinuclear antibodies in lymphopenia-induced autoimmunity2014

    • Author(s)
      Eri Toshiki, Kawahata Kimito, Imamura Mitsuru, Kanzaki Takeyuki, Akahira Lisa, Michishita Kazuya, Yamamoto Kazuhiko
    • Organizer
      第58回 日本リウマチ学会
    • Place of Presentation
      東京・グランドプリンスホテル新高輪
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2023-03-23  

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