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A mechanistic analysis of Trm competition for epidermal niche

Research Project

Project/Area Number 21K15468
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Hirai Toshiro  大阪大学, 微生物病研究所, 特任講師(常勤) (00895815)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsT細胞 / 皮膚 / 組織局在型T細胞
Outline of Research at the Start

組織局在型記憶T細胞(Trm)は、抹消組織に局在する記憶T細胞であり、その高い感染防御能からワクチン開発等で注目されている。申請者はこれまでに、独自の皮膚Trmモデルを 用いて、Trmが組織内で維持される数に上限があることを示し、新規免疫誘導が、過去の免疫記憶を失わせてしまう可能性を明らかとした。本申請研究では、このT細胞間のニッチ競合の機序を、T細胞間の直接相互作用の観点から明らかとしたい。 本申請研究を通じて、T細胞間の競合を制御することができれば、安全で有効なワクチン開発を促進するほか、Trmの関わるがんや自己免疫疾患等の治療に新たな切り口を提供することにもつながると考えられる。

Outline of Final Research Achievements

Tissue-resident memory T cells (Trm) are the non-circulating subset of memory T cells. It has been suggested that there is an upper limit to the number of Trm maintained in epidermis and that recruitment of new T cells clones into epidermis may result in the loss of past immune memory. Elucidating the mechanism of competition of Trm for epidermal niche, we analyzed roles of CD86 on Trm in steady state and during proliferation followed by re-encounter to specific antigen.

Academic Significance and Societal Importance of the Research Achievements

Trmは、高い感染防御能を示すとともに、アレルギーや自己免疫疾患では病原性を示す。Trm同士の維持ニッチをめぐる競合機序に関する知見は、Trmの誘導や維持に関する機序を理解することにつながる。そのため、Trmをより効率よく誘導するワクチンの開発や、Trmが重要な病原性因子となるアレルギーや自己免疫疾患の新規治療法の開発等に役立つと考えられる。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (5 results)

All 2022 Other

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

  • [Int'l Joint Research] University of Pittsburgh(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Pittsburgh(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Competition between T Cells for a Finite Epidermal Niche Promotes Selective Retention of Antigen-specific Memory T Cells in the Epidermis2022

    • Author(s)
      Hirai Toshiro
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 142 Issue: 12 Pages: 1327-1332

    • DOI

      10.1248/yakushi.22-00155

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2022-12-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses2022

    • Author(s)
      Hirai Toshiro、Yoshioka Yasuo
    • Journal Title

      Frontiers in Immunology

      Volume: 13

    • DOI

      10.3389/fimmu.2022.918611

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] TGFb活性化をめぐるT細胞間競合が形作る皮膚免疫記憶2022

    • Author(s)
      平井敏郎
    • Organizer
      第72回日本薬学会関西支部総会・大会
    • Related Report
      2022 Annual Research Report
    • Invited

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Published: 2021-04-28   Modified: 2024-01-30  

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