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Epigenetic regulation of T cell senescence

Research Project

Project/Area Number 19K23850
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0803:Pathology, infection/immunology, and related fields
Research InstitutionKeio University

Principal Investigator

Nagai Nao  慶應義塾大学, 医学部(信濃町), 特任助教 (80828145)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsT細胞 / 疲弊 / 老化 / エピジェネティクス / 転写制御 / がん
Outline of Research at the Start

免疫系の機能低下は、加齢や疾患に伴う個体の機能低下に極めて重要な役割を果たしており、健康長寿社会の実現に向けて克服すべき課題である。免疫系の中心を担うT細胞は、加齢に伴って「老化(senescence)」と呼ばれる機能異常状態に陥り、このことが免疫力の低下や疾患の原因となる。しかしながら、T細胞が老化するメカニズムの詳細はわかっていない。
本研究では、エピジェネティクスと呼ばれる生命現象に注目し、T細胞の老化メカニズムを解明することを目的とする。また、T細胞の老化が個体機能やがんなどの疾患の病態に与える影響を解析するとともに、T細胞の老化を解除する方法を開発する。

Outline of Final Research Achievements

It has been widely recognized that T cells, which play a central role in the immune system, become dysfunctional with aging and diseases (termed “senescence” and “exhaustion”, respectively). In this study, we analyzed this mechanism using advanced technologies such as next-generation sequencers and bioinformatics. As a result, we found one candidate gene that is involved in exhaustion of CD8-positive T cells, which are responsible for anti-tumor immunity, in tumors.

Academic Significance and Societal Importance of the Research Achievements

加齢に伴うT細胞の老化は、易感染性やワクチンに対する応答性の低下を引き起こす。また、がんにおけるT細胞の疲弊は、抗腫瘍免疫の低下による腫瘍の進展に関わる。T細胞の疲弊に関わる候補遺伝子を発見したことは、新規のがん免疫療法を開発したり、昨今注目を浴びる免疫チェックポイント阻害剤の治療効果を最大化する戦略を開発したりすることに結びつく。また、この遺伝子が老化と疲弊に共通して重要である場合には、加齢に伴う免疫応答の低下に対する予防・治療方法の開発にもつながる。

Report

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

    (4 results)

All 2021 2020

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results)

  • [Journal Article] Immunomodulation by Inflammation during Liver and Gastrointestinal Tumorigenesis and Aging2021

    • Author(s)
      Nao Nagai, Yotaro Kudo, Daisuke Aki, Hayato Nakagawa, Koji Taniguchi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 5 Pages: 2238-2238

    • DOI

      10.3390/ijms22052238

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysine demethylase 7a regulates murine anterior-posterior development by modulating the transcription of Hox gene cluster2020

    • Author(s)
      Higashijima Yoshiki、Nagai Nao、Yamamoto Masamichi、Kitazawa Taro、Kawamura Yumiko K.、Taguchi Akashi、Nakada Natsuko、Nangaku Masaomi、Furukawa Tetsushi、Aburatani Hiroyuki、Kurihara Hiroki、Wada Youichiro、Kanki Yasuharu
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 725-725

    • DOI

      10.1038/s42003-020-01456-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The NOTCH-FOXM1 Axis Plays a Key Role in Mitochondrial Biogenesis in the Induction of Human Stem Cell Memory-like CAR-T Cells.2020

    • Author(s)
      Kondo T, Ando M, Nagai N, Tomisato W, Srirat T, Liu B, Mise-Omata S, Ikeda M, Chikuma S, Nishimasu H, Nureki O, Ohmura M, Hayakawa N, Hishiki T, Uchibori R, Ozawa K, Yoshimura A
    • Journal Title

      Cancer Res

      Volume: 80 Issue: 3 Pages: 471-483

    • DOI

      10.1158/0008-5472.can-19-1196

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells2020

    • Author(s)
      Higashijima Y, Matsui Y, Shimamura T, Nakaki R, Nagai N, Tsutsumi S, Abe Y, Link VM, Osaka M, Yoshida M, Watanabe R, Tanaka T, Taguchi A, Miura M, Ruan X, Li G, Inoue T, Nangaku M, Kimura H, Furukawa T, Aburatani H, Wada Y, Ruan Y, Glass CK, Kanki Y
    • Journal Title

      The EMBO Journal

      Volume: 39 Issue: 7 Pages: 1-1

    • DOI

      10.15252/embj.2019103949

    • NAID

      120006902140

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2019-09-03   Modified: 2022-01-27  

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