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ThPOK represses CXXC5, which inhibits CD40L expression in cytotoxic T cells through epigenetic regulation

Research Project

Project/Area Number 25460401
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionNational Center for Geriatrics and Gerontology

Principal Investigator

Naoe Yoshinori  国立研究開発法人国立長寿医療研究センター, 運動器疾患研究部, 流動研究員 (50392048)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsヘルパーT細胞 / 細胞障害性T細胞 / ThPOK / CXXC5 / エピジェネティクス / T細胞 / T細胞 / Cxxc5
Outline of Final Research Achievements

CD40L is induced in helper T cells upon TCR stimulation. However, the mechanisms whereby CD40L becomes expressed in T cells remain unclear. We showed that CD40L expression in cytotoxic T cells was suppressed by combined epigenetic regulations in the promoter of the Cd40lg gene such as the methylation of CpG dinucleotides, histone H3 lysine 9 (H3K9), H3K27, and H4K20. As ThPOK is critical in helper T cell development, we focused on the role of ThPOK in CD40L expression. CD40L expression is moderately induced by retroviral Thpok transduction into cytotoxic T cells, which was accompanied by a reduction of H3K9 methylation (H3K9me) and H4K20me in the promoter of the Cd40lg gene. ThPOK directly inhibited the expression of CXXC5 that induced H3K9me through an interaction with SUV39H1. In addition to inhibit CD40L induction in activated helper T cells by CXXC5, our findings indicate that CXXC5 was one of the key molecules contributing to repressing CD40L expression in cytotoxic T cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2016 2015 2013

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

  • [Journal Article] ThPOK represses CXXC5, which induces methylation of histone H3 lysine 9 in Cd40lg promoter by association with SUV39H1: implications in repression of CD40L expression in CD8+ cytotoxic T cells2016

    • Author(s)
      Tsuchiya Y, Naito T, Tenno M, Maruyama M, Koseki H, Taniuchi I, Naoe Y.
    • Journal Title

      J Leukoc Biol.

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Proliferation-coupled osteoclast differentiation by RANKL: Cell density as a determinant of osteoclast formation.2015

    • Author(s)
      Motiur Rahman M, Takeshita S, Matsuoka K, Kaneko K, Naoe Y, Sakaue-Sawano A, Miyawaki A, Ikeda K.
    • Journal Title

      Bone.

      Volume: 81 Pages: 392-399

    • DOI

      10.1016/j.bone.2015.08.008

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A novel Cd8-cis-regulatory element preferentially directs expression in CD44hiCD62L+ CD8+ T cells and in CD8αα+ dendritic cells.2015

    • Author(s)
      Sakaguchi S, Hombauer M, Hassan H, Tanaka H, Yasmin N, Naoe Y, Bilic I, Moser MA, Hainberger D, Mayer H, Seiser C, Bergthaler A, Taniuchi I, Ellmeier W.
    • Journal Title

      J Leukoc Biol.

      Volume: 97 Issue: 4 Pages: 635-644

    • DOI

      10.1189/jlb.1hi1113-597rr

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation.2013

    • Author(s)
      Kitamura et al.
    • Journal Title

      FASEB J.

      Volume: 27 Issue: 12 Pages: 4940-4953

    • DOI

      10.1096/fj.13-233528

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Beneficial effects of Brazilian propolis on type 2 diabetes in ob/ob mice: Possible involvement of immune cells in mesenteric adipose tissue2013

    • Author(s)
      Kitamura H, Naoe Y, Kimura S, Miyamoto T, Okamoto S, Toda C, Shimamoto Y, Iwanaga T, Miyoshi I
    • Journal Title

      Adipocyte

      Volume: 2 Issue: 4 Pages: 227-236

    • DOI

      10.4161/adip.25608

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Cxxc5, ThPOK target gene, suppresses CD4+ helper T cell functions during CD8+cytotoxic T differentiation2013

    • Author(s)
      直江吉則、内藤拓、天野麻理、丸山光生、古関明彦、谷内一郎
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      千葉
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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