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Negative selection of T cells by the factor suppressing autoimmunity

Research Project

Project/Area Number 16H06228
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionThe University of Tokyo

Principal Investigator

Takaba Hiroyuki  東京大学, 大学院医学系研究科(医学部), 助教 (50637444)

Research Collaborator Takayanagi hiroshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2017: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2016: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywords免疫寛容 / 獲得免疫 / T細胞 / 中枢免疫寛容 / 中枢寛容 / 自己免疫 / T細胞の選択
Outline of Final Research Achievements

T cells are one of the most important population for adaptive immune system. It is well known that T cells are generated in the thymus and the autoantigens are produced by medullary thymic epithelial cells expressing two transcriptional regulators Aire and Fezf2. In this study, we characterized the distinct features of Fezf2-dependent and Aire-dependent genes expressed in mTECs. Single cell RNA-seq analysis revealed the different expression pattern between Aire-dependent and Fezf2-dependent genes among mTECs. Our study suggest that the expression level of autoantigens might be key for the negative selection of T cells and regulatory T cell differentiation in the thymus to establish immune tolerance.

Academic Significance and Societal Importance of the Research Achievements

免疫寛容の破綻は、自己免疫疾患やアレルギー疾患を引き起こし、日常生活に大きな支障をきたす。自己免疫疾患の患者は、日本国内だけでも数百万人いると見積もられている。免疫疾患の患者数は年々増加の一途を辿り、社会的にも深刻な問題であり、根本的な治療法の確立が喫緊の課題である。自己抗原が特定されていない自己免疫疾患は多くあり、自己抗原を認識するT細胞の集団とその抗原を同定することは自己免疫疾患の根本的治療に関わる。自己抗原は胸腺内でストローマ細胞のmTECで主に発現しており、この分子基盤の解明が将来的に自己免疫の効率的な治療法の開発に繋がる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (8 results)

All 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Book (1 results)

  • [Int'l Joint Research] MIT(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] The mechanisms of T cell selection in the thymus2017

    • Author(s)
      Hiroyuki Takaba and Hiroshi Takayanagi
    • Journal Title

      Trends in immunology

      Volume: 38, 11 Issue: 11 Pages: 805-8016

    • DOI

      10.1016/j.it.2017.07.010

    • NAID

      40021132352

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Self-Reflection by Tolerogenic Factors: Promiscuous Gene Expression in the Thymus2018

    • Author(s)
      Hiroyuki Takaba
    • Organizer
      Japanese Society for Immunology(JSI)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Epigenetic regulation of thymic self-antigen expression for immune tolerance2018

    • Author(s)
      Hiroyuki Takaba, Yoshihiko Tomofuji, Hiroshi Takayanagi
    • Organizer
      Gordon conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinct features of Fezf2-dependent promiscuous gene expression2018

    • Author(s)
      Yoshihiko Tomofuji, Hiroyuki Takaba and Hiroshi Takayanagi
    • Organizer
      ThymOZ8
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] T cell selection mediated by Fezf2 in the thymus2017

    • Author(s)
      Hiroyuki Takaba and Hiroshi Takayanagi
    • Organizer
      KTCC 2017
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 免疫学のセントラルドグマ2017

    • Author(s)
      高場啓之
    • Organizer
      Conbio2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Book] 胸腺におけるT細胞の選択機構2017

    • Author(s)
      高場啓之、高柳広
    • Total Pages
      6
    • Publisher
      臨床免疫・アレルギー科
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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