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Analysis of autoimmune diseases pathogenesis with a novel reporter system

Research Project

Project/Area Number 16KT0114
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund
Section特設分野
Research Field Complex Systems Disease Theory
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

Sekiya Takashi  国立研究開発法人国立国際医療研究センター, その他部局等, 免疫応答修飾研究室長 (80519207)

Project Period (FY) 2016-07-19 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords免疫学 / 制御性T細胞 / 生体イメージング / CD4T細胞 / in vivoレポーター / 自己免疫疾患 / T細胞 / レポーターシステム / 免疫寛容 / アレルギー・ぜんそく
Outline of Final Research Achievements

Helper T cells (Th) and regulatory T cells (Treg) play important roles in preventing false immune responses and activating the correct immune response depending on the type of antigen. It can be said that research on Th and Treg in the early stage of differentiation was delayed, but one of the main reasons for this is thought to be that a powerful system for detecting Th and Treg in the early stage of differentiation in vivo has not been established.
Therefore, in this study, we constructed a new reporter system that can monitor Th and Treg at the differentiation stage in vivo minimally invasively and can be isolated and analyzed as living cells, and we analyzed the pathogenesis of human multiple sclerosis mouse model EAE. By the analysis describing above, We succeeded in capturing the activation of the immune response during the course of EAE pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

分化初期段階のThやTregの研究は遅れていたと言えるが、本研究により、分化初期段階にあるThやTregをin vitro, in vivoの両方で検出できる強力な実験システムを構築することに成功した。このレポーターマウスは将来的に多くの研究組織にdistributeされ、様々な疾患を対象に解析されることで、炎症性疾患のみならず、多くの疾患の発症機構の解明、ひいては新規治療法の開発に寄与されると期待される。さらに本研究は、ヒト多発性硬化症マウスモデルEAEの解析により、既知の免疫応答のみならず、腸管や口腔など、解析の進んでいない部位からの免疫応答を検出しており、今後の研究展開に期待が持たれる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2019 2018 2017 2016

All Journal Article (7 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (3 results)

  • [Journal Article] RGMB enhances the suppressive activity of the monomeric secreted form of CTLA-42019

    • Author(s)
      Sekiya Takashi, Takaki Satoshi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 6984-6984

    • DOI

      10.1038/s41598-019-43068-y

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity2019

    • Author(s)
      Lyszkiewicz Marcin, Takashi Sekiya, Andreas Krueger et al.
    • Journal Title

      PLOS Biology

      Volume: 17 Issue: 3 Pages: e2006716-e2006716

    • DOI

      10.1371/journal.pbio.2006716

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NR4A transcription factors limit CAR T cell function in solid tumours2019

    • Author(s)
      Chen Joyce、L?pez-Moyado Isaac F.、Seo Hyungseok、Lio Chan-Wang J.、Hempleman Laura J.、Sekiya Takashi、Yoshimura Akihiko、Scott-Browne James P.、Rao Anjana
    • Journal Title

      Nature

      Volume: 567 Issue: 7749 Pages: 530-534

    • DOI

      10.1038/s41586-019-0985-x

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nr4a Receptors Regulate Development and Death of Labile Treg Precursors to Prevent Generation of Pathogenic Self-Reactive Cells2018

    • Author(s)
      Takashi Sekiya、Hibino Sana、Saeki Keita、Kanamori Mitsuhiro、Takaki Satoshi、Yoshimura Akihiko
    • Journal Title

      Cell Reports

      Volume: 24 Issue: 6 Pages: 1627-1638.e6

    • DOI

      10.1016/j.celrep.2018.07.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of alloantigen-specific induced-Treg stabilized by vitamin C treatment and its application for prevention of acute graft versus host disease model2017

    • Author(s)
      Hidenori Kasahara, Taisuke Kondo, Hiroko Nakatsukasa, Shunsuke Chikuma, Minako Ito, Makoto Ando, Yutaka Kurebayashi, Takashi Sekiya, Taketo Yamada, Shinichiro Okamoto, Akihiko Yoshimura
    • Journal Title

      International Immunology

      Volume: 29 Issue: 10 Pages: 457-469

    • DOI

      10.1093/intimm/dxx060

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy2017

    • Author(s)
      Taisuke Kondo, Rimpei Morita, Yuumi Okuzono, Hiroko Nakatsukasa, Takashi Sekiya, Shunsuke Chikuma, Takashi Shichita, Mitsuhiro Kanamori, Masato Kubo, Keiko Koga, Takahiro Miyazaki, Yoshiaki Kassai, Akihiko Yohimura
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 15338-15338

    • DOI

      10.1038/ncomms15338

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of transcription factors and epigenetic modifications in differentiation and maintenance of regulatory T cells.2016

    • Author(s)
      Sekiya T, Nakatsukasa H, Lu Q, and Yoshimura A.
    • Journal Title

      Microbes Infect.

      Volume: 18 Issue: 6 Pages: 378-386

    • DOI

      10.1016/j.micinf.2016.02.004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Roles of the nuclear orphan receptor Nr4a in Th/Treg differentiation and in regulation of allergic asthma pathogenesis2019

    • Author(s)
      Takashi Sekiya, Satoshi Takaki, and Akihiko Yoshimura
    • Organizer
      The 17th International Congress of Immunology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 制御性T細胞移入療法の進歩を導く基礎研究の現在2019

    • Author(s)
      関谷 高史
    • Organizer
      第55回 日本移植学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Nr4aファミリー転写因子によるCD4T細胞の分化制御2019

    • Author(s)
      関谷 高史
    • Organizer
      第28回 東京免疫フォーラム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Roles of the nuclear orphan receptor Nr4a in Th/Treg differentiation and in regulation of allergic asthma pathogenesis2018

    • Author(s)
      Takashi Sekiya, Satoshi Takaki, and Akihiko Yoshimura
    • Organizer
      日本免疫学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Nr4a receptors promote completion of Treg cell developmental program and prevent conversion of labile Treg precursors into pathogenic cells2016

    • Author(s)
      Takashi Sekiya and Akihiko Yoshimura
    • Organizer
      16th International Congress of Immunology
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] 医学のあゆみ 制御性T細胞研究の現在2019

    • Author(s)
      関谷 高史
    • Total Pages
      6
    • Publisher
      医歯薬出版
    • Related Report
      2019 Annual Research Report
  • [Book] 医学のあゆみ 制御性T細胞研究の現在2019

    • Author(s)
      関谷 高史
    • Total Pages
      6
    • Publisher
      医歯薬出版
    • Related Report
      2018 Research-status Report
  • [Book] Epigenetics of Autoimmunity2018

    • Author(s)
      Takashi Sekiya
    • Total Pages
      432
    • Publisher
      Elsevir
    • ISBN
      9780128099285
    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-07-20   Modified: 2023-03-08  

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