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Molecular mechanisms for CD4 T cell differentiation, aiming at generation of functional Treg cells

Research Project

Project/Area Number 26713019
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Immunology
Research InstitutionNational Center for Global Health and Medicine (2016)
Keio University (2014-2015)

Principal Investigator

Sekiya Takashi  国立研究開発法人国立国際医療研究センター, その他部局等, 室長 (80519207)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2014: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
KeywordsCD4T細胞 / 免疫寛容 / 制御性T細胞 / エピジェネティクス / 免疫学 / 自己免疫疾患 / T細胞
Outline of Final Research Achievements

By classifying Treg precursor cells according to their developmental stages, we revealed Treg cell developmental programs which are dependent on Nr4a factors, as well as programs that are independent of Nr4a factors. In the analysis, we further elucidated that Nr4a factors act at relatively later stages in Treg cell development. Foxp3, that were induced by Nr4a factors then found to induce Nr4a factors, thus forming a positive feedback loop, sustaining Treg cell development.Furthermore, Nr4a-deficient Treg precursor cells not only complete their development to Treg cells, but they survive with an attenuated expression of apoptotic factors including Bim, thus converting to helper-T like cells with elevated expression of inflammatory cytokines that are usually not to be expressed by Treg cells but by helper T cells.

Report

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

    (6 results)

All 2016 2015 2014

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Roles of transcription factors and epigenetic modifications in differentiation and maintenance of regulatory T cells.2016

    • Author(s)
      Sekiya T, Nakatsukasa H, Lu Q, and Yoshimura A.
    • Journal Title

      Microbes Infect.

      Volume: 18 Issue: 6 Pages: 378-386

    • DOI

      10.1016/j.micinf.2016.02.004

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Suppression of Th2 and Tfh immune reactions by Nr4a receptors in mature T reg cells2015

    • Author(s)
      Sekiya T, Kondo T, Shichita T, Morita R, Ichinose H, Yoshimura A
    • Journal Title

      J Exp Med.

      Volume: 212 Issue: 10 Pages: 1623-1640

    • DOI

      10.1084/jem.20142088

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Innate-like function of memory Th17 cells for enhancing endotoxin-induced acute lung inflammation through IL-22.2015

    • Author(s)
      Sakaguchi R, Chikuma S, Shichita T, Morita R, Sekiya T, Ouyang W, Ueda T, Seki H, Morisaki H, Yoshimura A
    • Journal Title

      Int Immunol.

      Volume: 28 Issue: 5 Pages: 233-243

    • DOI

      10.1093/intimm/dxv070

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ETS transcription factor ETV2 directly converts human fibroblasts into functional endothelial cells.2015

    • Author(s)
      Morita R, Suzuki M, Kasahara H, Shimizu N, Shichita T, Sekiya T, Kimura A, Sasaki K, Yasukawa H, Yoshimura A.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 112 Issue: 1 Pages: 160-165

    • DOI

      10.1073/pnas.1413234112

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Aryl hydrocarbon receptor protects against bacterial infection by promoting macrophage survival and reactive oxygen species production2014

    • Author(s)
      Kimura A, Abe H, Tsuruta S, Chiba S, Fujii-Kuriyama Y, Sekiya T, Morita R, Yoshimura A.
    • Journal Title

      Int Immunol.

      Volume: 26 Issue: 4 Pages: 209-220

    • DOI

      10.1093/intimm/dxt067

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Nr4a receptors promote completion of Treg cell developmental program and prevent conversion of labile Treg precursors into pathogenic cells2016

    • Author(s)
      Takashi Sekiya and Akihiko Yoshimura
    • Organizer
      16th International Congress of Immunology
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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

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