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The role of TET proteins in stability and function of regulatory T cells.

Research Project

Project/Area Number 15K19135
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionKeio University

Principal Investigator

Nakatsukasa Hiroko  慶應義塾大学, 医学部(信濃町), 特別研究員(PD) (90749334)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords制御性T細胞 / エピジェネティクス / 自己免疫疾患 / TET
Outline of Final Research Achievements

Regulatory T cells (Tregs) play a pivotal role in regulating immune responses and maintaining immunological tolerance. Although DNA demethylation has been proposed to be essential for the stable expression of Foxp3, a master regulator of Treg, actual contribution of DNA demethylating enzymes (Tet family proteins) in Treg stability and function remain to be elucidated. In this study, we analyzed T cell- or Treg-specific Tet2/3-deficient mice and found that Tet2/3 play important roles in the differentiation, stability and function of T cells and Tregs through regulating DNA demethylation. Furthermore, we have successfully induced region-specific demethylation in Foxp3 gene locus.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2017 2016

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 (7 results) (of which Int'l Joint Research: 4 results) Book (3 results)

  • [Journal Article] Stabilization of Foxp3 expression by CRISPR-dCas9-based epigenome editing in mouse primary T cells.2017

    • Author(s)
      Okada M, Kanamori M, Someya K, Nakatsukasa H and Yoshimura A.
    • Journal Title

      Epigenetics & Chromatin

      Volume: 印刷中 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s13072-017-0129-1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy.2017

    • Author(s)
      Kondo T, Morita R, Okuzono Y, Nakatsukasa H, Sekiya T, Chikuma S, Shichita T, Kanamori M, Kubo M, Koga K, Miyazaki T, Kassai Y, and Yoshimura A.
    • Journal Title

      Nat Commun.

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of ATP as a Key Signaling Molecule Mediating Radiation-Induced Biological Effects.2017

    • Author(s)
      Kojima S, Ohshima Y, Nakatsukasa H, Tsukimoto M.
    • Journal Title

      Dose Response.

      Volume: 15 Issue: 1 Pages: 1-11

    • DOI

      10.1177/1559325817690638

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induced Regulatory T Cells: Their Development, Stability, and Applications.2016

    • Author(s)
      Kanamori M, Nakatsukasa H, Okada M, Lu Q, Yoshimura A.
    • Journal Title

      Trends Immunol.

      Volume: 37 Issue: 11 Pages: 803-811

    • DOI

      10.1016/j.it.2016.08.012

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] TET2 and TET3 regulate stability and homeostasis of regulatory T cells.2017

    • Author(s)
      Nakatsukasa H and Yoshimura A.
    • Organizer
      第19回武田科学振興財団生命科学シンポジウム
    • Place of Presentation
      武田薬品研修所(大阪府吹田市)
    • Year and Date
      2017-01-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TET2 and TET3 regulate Treg stability through Treg-specific DNA demethylation.2017

    • Author(s)
      Nakatsukasa H and Yoshimura A.
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      タオス(アメリカ)
    • Year and Date
      2017-01-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TET2 and TET3 play essential roles in Treg-specific DNA demethylation and Treg stability.2016

    • Author(s)
      Nakatsukasa H and Yoshimura A.
    • Organizer
      International Congress of Immunology 2016
    • Place of Presentation
      メルボルン(オーストラリア)
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TET2 and TET3 play essential roles in Treg-specific DNA demethylation and Treg stability2016

    • Author(s)
      中司寛子
    • Organizer
      International Congress of Immunology 2016
    • Place of Presentation
      メルボルン(オーストラリア)
    • Year and Date
      2016-08-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 制御性T細胞のDNA脱メチル化による制御2016

    • Author(s)
      中司寛子、吉村昭彦
    • Organizer
      第1回Clinical Immunology/Inflammation Seminar in Shinanomachi
    • Place of Presentation
      慶應義塾大学(東京都新宿区)
    • Year and Date
      2016-07-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 制御性T細胞のヒドロキシメチル化による制御2016

    • Author(s)
      中司寛子
    • Organizer
      第2回病因研究会別府シンポジウム
    • Place of Presentation
      別府湾ロイヤルホテル(大分県速見郡)
    • Year and Date
      2016-02-06
    • Related Report
      2015 Research-status Report
  • [Presentation] T細胞特異的Tet2,Tet3遺伝子欠損マウスの解析2016

    • Author(s)
      中司寛子
    • Organizer
      AMED-CREST「エピゲノム研究に基づく診断・治療へ向けた新技術の創出」研究開発領域第5回領域会議
    • Place of Presentation
      メルパルク熊本(熊本県熊本市)
    • Year and Date
      2016-01-06
    • Related Report
      2015 Research-status Report
  • [Book] 臨床免疫・アレルギー科2017

    • Author(s)
      中司寛子
    • Total Pages
      6
    • Publisher
      科学評論社
    • Related Report
      2016 Annual Research Report
  • [Book] 実験医学増刊2016

    • Author(s)
      吉村昭彦、岡田匡央、金森光広、中司寛子
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2016 Annual Research Report
  • [Book] 臨床免疫・アレルギー科2016

    • Author(s)
      中司寛子、金森光広、岡田匡央、吉村昭彦
    • Total Pages
      7
    • Publisher
      科学評論社
    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2018-03-22  

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