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The regulation of memory B cell by DNA demethylation

Research Project

Project/Area Number 16K08738
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionKyushu University (2018)
Tokyo University of Science (2017)
Osaka University (2016)

Principal Investigator

TANAKA SHINYA  九州大学, 生体防御医学研究所, 助教 (80462703)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsDNA methylation / Ten-Eleven Translocation / B cells / DNA demethylation / Self tolerance / Ten-Eleven translocation / B細胞分化 / B細胞ホメオスターシス / B細胞自己寛容 / 能動的DNA脱メチル化
Outline of Final Research Achievements

DNA methylation is an well-known epigenetic modification to regulate differentiation and function of multiple linage cells. However, it has been unknown that how the modification regulates the B cell biology. In the current study, we demonstrated that a DNA demethylase, Ten-Eleven Translocation (Tet) prevented autoimmune disease by suppressing aberrant activation of B cells. In contrast, Tet molecules played a pivotal role in differentiation and/or maintenance of effector B cells such as plasma cells, germinal center B cells and memory B cells for appropriate humoral immune response. These data suggest that Tet molecules play a pleiotropic roles in differentiation and/or function of peripheral B cells.

Academic Significance and Societal Importance of the Research Achievements

B細胞は、抗体産生を担い生体防御に寄与する免疫細胞であるが、その制御が適切になされない場合は、自己免疫疾患の発症に寄与することが知られている。本研究によって、DNAメチル化制御因子であるTet分子が、B細胞の不適切な過剰活性化を抑制することにより、自己免疫疾患の発症を防ぐ役割を担っていることが明らかとなった。Tet分子活性の人為的操作によって、B細胞が原因となる自己免疫疾患のみならず、ウィルス、バクテリア感染時のB細胞の活性を制御することで液性免疫応答を調節するための新たな標的としての可能性が示唆された。

Report

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

    (5 results)

All 2018

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

  • [Journal Article] Trim33 mediates the proinflammatory function of Th17 cells.2018

    • Author(s)
      Tanaka S, Jiang Y, Martinez GJ, Tanaka K, Yan X, Kurosaki T, Kaartinen V, Feng XH, Tian Q, Wang X, Dong C
    • Journal Title

      Journal of Experimental Medicine

      Volume: 215 Pages: 1853-1868

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of Pathogenic T Helper 17 Cell Differentiation by Steroid Receptor Coactivator-32018

    • Author(s)
      Tanaka K, Martinez GJ, Yan X, Long W, Ichiyama K, Chi X, Kim BS, Reynolds JM, Chung Y, Tanaka S, Liao L, Nakanishi Y, Yoshimura A, Zheng P, Wang X, Tian Q, Xu J, O'Malley BW, Dong C
    • Journal Title

      Cell reports

      Volume: 23 Pages: 2318-2329

    • Related Report
      2018 Annual Research Report
  • [Presentation] Ten-eleven translocation (Tet) demethylases mediate peripheral B cell tolerance2018

    • Author(s)
      SHINYA TANAKA
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] B cell-mediated inflammation by epigenetic regulators2018

    • Author(s)
      SHINYA TANAKA
    • Organizer
      2018 Fall International Convention of The Pharmaceutical Society of Korea
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Ten-eleven translocation (Tet) DNA demethylases maintain peripheral B cell tolerance2018

    • Author(s)
      SHINYA TANAKA
    • Organizer
      第10回 シグナルネットワーク研究会
    • Related Report
      2018 Annual Research Report

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

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