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Elucidation of novel molecular mechanisms of early T cell development by regulation of intracellular ion homeostasis

Research Project

Project/Area Number 18K07178
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionJuntendo University

Principal Investigator

Masatsugu Oh-hora  順天堂大学, 医学(系)研究科(研究院), 先任准教授 (40351506)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsT細胞分化 / イオンチャネル / シグナル情報伝達 / betaセレクション / βセレクション / T細胞 / 初期分化
Outline of Final Research Achievements

Ions are required for T cell development and function. In this study, we focused on TRPM7, which is a non-selective divalent cation channel and highly expressed in immature thymocytes. In lymphocyte-specific TRPM7 deficient mice, TRPM7 is required for cell proliferation and survival in immature thymocytes. In addition, we have found that expressions of genes upregulated after beta-selection was downregulated by TRPM7 deficiency. Among these genes, a novel RNA-binding molecule was selectively expressed in immature thymocytes. In order to elucidate the roles of this molecule in T cell development, we have established the knockout mouse.

Academic Significance and Societal Importance of the Research Achievements

T細胞は免疫系の司令塔であり、その活性化や分化の仕組みを理解することは、アレルギー治療や感染防御の観点から重要な課題である。また、健康を維持するために必要な栄養素である必須ミネラルは、体内ではイオンとして存在する。本研究では、カルシウム、マグネシウム、亜鉛など透過するイオンチャネルがT細胞の分化に必須であることを明らかにした。この成果は、イオンチャネルの機能異常を特徴とする病態機序を理解する上でも重要であり、免疫疾患におけるイオンチャネルを標的とする創薬開発への貢献が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2019

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

  • [Journal Article] Stromal Interaction Molecule Deficiency in T Cells Promotes Spontaneous Follicular Helper T Cell Development and Causes Type 2 Immune Disorders2019

    • Author(s)
      Oh-hora Masatsugu、Lu Xiuyuan、Shiokawa Moe、Takayanagi Hiroshi、Yamasaki Sho
    • Journal Title

      The Journal of Immunology

      Volume: 0 Issue: 9 Pages: 2616-2627

    • DOI

      10.4049/jimmunol.1700610

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pivotal role of STIM2, but not STIM1, in IL-4 production by IL-3?stimulated murine basophils2019

    • Author(s)
      Yoshikawa Soichiro、Oh-hora Masatsugu、Hashimoto Ryota、Nagao Toshihisa、Peters Louis、Egawa Mayumi、Ohta Takuya、Miyake Kensuke、Adachi Takahiro、Kawano Yohei、Yamanishi Yoshinori、Karasuyama Hajime
    • Journal Title

      Science Signaling

      Volume: 12 Issue: 576

    • DOI

      10.1126/scisignal.aav2060

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Stim-deficiency in T cells promotes spontaneous follicular T cell development and causes type 2 immune disorders2019

    • Author(s)
      Oh-hora M, Lu X, Shiokawa M, Takayanagi H, Yamasaki S.
    • Organizer
      FASEB Science research conferences
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Book] 医学のあゆみ2019

    • Author(s)
      大洞将嗣
    • Total Pages
      251
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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