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Analysis of epigenetic regulatory mechanisms of Th17 differentiation

Research Project

Project/Area Number 16K19164
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionOkinawa Institute of Science and Technology Graduate University

Principal Investigator

Ishikawa Hiroki  沖縄科学技術大学院大学, 免疫シグナルユニット, 准教授 (30648621)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsTh17細胞 / 分化 / 病原性 / T細胞 / 自己免疫疾患 / エピジェネティック制御 / ヘルパーT細胞
Outline of Final Research Achievements

IL-17-producing Th17 cells comprise heterogeneous subsets exhibiting distinct pathogenicity. Although pathogenic and non-pathogenic Th17 subsets share a common Th17 transcriptional program composed of BATF, IRF4, STAT3, and RORgt, transcriptional regulatory mechanisms specific to each of these distinct Th17 subsets remain largely unknown. Here we show that an AP-1 transcription factor, JunB, is essential for induction of RORgt by facilitating DNA-binding of BATF, IRF4 and STAT3 at the Rorc locus in IL-23-dependent pathogenic Th17 cells, but not in TGF-b1-dependent non-pathogenic Th17 cells. Indeed, JUNB deficient T cells lose their ability to induce Th17-mediated experimental autoimmune encephalomyelitis (EAE) and colitis, but gut-resident Th17 cells are probably generated in a JUNB-independent manner. The selective requirement of JUNB for pathogenic Th17 differentiation suggests that the JUNB-dependent pathway may be a specific therapeutic target for autoimmune diseases.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2017

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

  • [Journal Article] JunB is essential for IL-23-dependent pathogenicity of Th17 cells.2017

    • Author(s)
      Hasan Z, Koizumi SI, Sasaki D, Yamada H, Arakaki N, Fujihara Y, Okitsu S, Shirahata H, Ishikawa H
    • Journal Title

      Nature communications

      Volume: 8 Pages: 15628-15628

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] JunB-dependent regulation of Th17 pathogenicity.2017

    • Author(s)
      Hiroki Ishikawa
    • Organizer
      The 2nd Design Biology Engineering Study Group Meeting
    • Place of Presentation
      兵庫県、神戸ポートアイランド
    • Year and Date
      2017-03-21
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] JunB-dependent generation of pathogenic Th17 cells2017

    • Author(s)
      Hiroki Ishikawa
    • Organizer
      24th East Asia Joint Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] STING: a new adjuvant target2017

    • Author(s)
      Hiroki Ishikawa
    • Total Pages
      6
    • Publisher
      CMC
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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