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Molecular mechanisms of immune memory maintenance corresponding to the risk of reinfection

Research Project

Project/Area Number 20K21356
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 42:Veterinary medical science, animal science, and related fields
Research InstitutionHokkaido University

Principal Investigator

TAKADA KENSUKE  北海道大学, 獣医学研究院, 准教授 (40570073)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords免疫記憶 / T細胞 / 生体防御
Outline of Research at the Start

再感染が起きなければ記憶Tリンパ球は徐々に減少する。このことは従来、生体防御に不都合なことと考えられてきた。しかし、定常状態で体内に維持できるTリンパ球数は限られるため、再感染リスクの低い病原体に対する記憶の低下は、免疫多様性を保持するための合理的な現象とも捉えられる。本研究は、感染から長期間を経た記憶Tリンパ球で特異的に発現される新規転写因子Dmrt4の機能解析を通じ、「再感染リスクに応じた免疫記憶維持」という新たな概念の提唱を目指す。本研究の成果はまた、Dmrt4を標的として、一度の接種により一生涯効果が持続する画期的なワクチン戦略の創出につながり得る。

Outline of Final Research Achievements

The detailed mechanism of immunological memory, which is the basic principle of vaccines, has not yet been elucidated. The body of immunological memory is the memory lymphocytes that are maintained in the body for a long period of time after antigen-specific activation. Dmrt4 is a novel transcription factor and its involvement in the immune system has not been reported. In this study, based on our own finding that Dmrt4 is highly expressed in CD8 + memory T lymphocytes, we investigated the role of Dmrt4 in memory T lymphocytes. Through this research project, we have obtained potentially interesting preliminary findings that will lead to future development of the research. However, it is still necessary to fully confirm the reproducibility of the experimental results regarding the effects on the phenotype, function and gene expression of memory T lymphocytes.

Academic Significance and Societal Importance of the Research Achievements

過去に感染した病原体の再感染に対し、免疫系はより素早く強力に応答する(免疫記憶)。免疫記憶の本体は抗原特異的な応答の後、体内で長期間維持される記憶リンパ球である。とりわけCD8+ 記憶Tリンパ球は、ウイルスや細菌、腫瘍細胞に対する防御に重要な役割を果たす。本研究から、免疫系での役割が不明な新規転写因子がCD8+ 記憶Tリンパ球の制御に関与する可能性が示唆された。現時点では予備的知見の域を出ないものの、今後検討を重ねることで、免疫記憶の基本原理の解明とともにワクチンや免疫療法の開発に貢献することが期待される。

Report

(2 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2021 2020

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results)

  • [Journal Article] The thymoproteasome hardwires the TCR repertoire of CD8+ T cells in the cortex independent of negative selection2021

    • Author(s)
      Ohigashi Izumi、Frantzeskakis Melina、Jacques Alison、Fujimori Sayumi、Ushio Aya、Yamashita Fusano、Ishimaru Naozumi、Yin Da、Cam Margaret、Kelly Michael C.、Awasthi Parirokh、Takada Kensuke、Takahama Yousuke
    • Journal Title

      Journal of Experimental Medicine

      Volume: 218 Issue: 4

    • DOI

      10.1084/jem.20201904

    • NAID

      120007170553

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ROR agonist hampers the proliferation and survival of postactivated CD8+ T cells through the downregulation of cholesterol synthesis‐related genes2020

    • Author(s)
      Cai Zimeng、Ishibashi Taishin、Kozai Mina、Mita Hironobu、Wang Shangyi、Takada Kensuke、Inaba Mutsumi
    • Journal Title

      Immunology & Cell Biology

      Volume: 99 Issue: 3 Pages: 288-298

    • DOI

      10.1111/imcb.12406

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced Immunotherapeutic Efficacy of Anti?PD-L1 Antibody in Combination with an EP4 Antagonist2020

    • Author(s)
      Sajiki Yamato、Konnai Satoru、Cai Zimeng、Takada Kensuke、Okagawa Tomohiro、Maekawa Naoya、Fujisawa Sotaro、Kato Yukinari、Suzuki Yasuhiko、Murata Shiro、Ohashi Kazuhiko
    • Journal Title

      ImmunoHorizons

      Volume: 4 Issue: 12 Pages: 837-850

    • DOI

      10.4049/immunohorizons.2000089

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cholesterol-binding protein TSPO2 coordinates maturation and proliferation of terminally differentiating erythroblasts2020

    • Author(s)
      Kiatpakdee Benjaporn、Sato Kota、Otsuka Yayoi、Arashiki Nobuto、Chen Yuqi、Tsumita Takuya、Otsu Wataru、Yamamoto Akito、Kawata Reo、Yamazaki Jumpei、Sugimoto Yoshikazu、Takada Kensuke、Mohandas Narla、Inaba Mutsumi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 23 Pages: 8048-8063

    • DOI

      10.1074/jbc.ra119.011679

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2020-08-03   Modified: 2023-01-30  

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