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The significance of regulatory T cells in the brain

Research Project

Project/Area Number 19K16618
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionKyushu University

Principal Investigator

Ito Minako  九州大学, 生体防御医学研究所, 准教授 (70793115)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords脳梗塞 / 脳内炎症 / 制御性T細胞
Outline of Research at the Start

我々はマウス実験的脳虚血 (脳梗塞) モデルを用いて脳損傷後の炎症によって梗塞や神経症状が増悪化することを見出し報告してきた。発症2週間目以降の慢性期には多量のT細胞が浸潤しており極めて特殊な様相を示すことを見出した。特にTregが大量に蓄積し、ミクログリアやアストロサイトの過剰な活性化を制御して神経症状の回復に寄与することを明らかにしている。本研究においてその分子機構を明らかにする。この研究によって脳梗塞や脊髄損傷、あるいは多発性硬化症の増悪化の原因と制御方法の理解が進むものと期待される。

Outline of Final Research Achievements

More than two weeks after the onset of cerebral infarction, the brain of mice was infiltrated with a much larger number of T cells than in the acute phase, especially with a large accumulation of regulatory T cells (Treg). The brain Treg also showed brain-specific properties. In the EAE model, where both the spinal cord and brain are affected, the phenotypes of Treg in the spinal cord and brain are different, and the brain Treg are similar to those of Treg infiltrated in the infarcted brain. The brain Treg was close to the characteristics of the Treg infiltrated in the brain of cerebral infarction. These results suggest that tissue Treg may acquire properties depending on the environment of the localized tissue rather than the pathology.

Academic Significance and Societal Importance of the Research Achievements

脳梗塞後の脳内に存在する制御性T細胞は、損傷した組織を修復する働きを持っていることが分かった。このように脳組織の修復を促す脳特異的Tregを誘導するメカニズムを解明することで新規治療法を開発出来る可能性がある。

Report

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

    (11 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Tocilizumab monotherapy uncovered the role of the CCL22/17-CCR4+ Treg axis during remission of crescentic glomerulonephritis2020

    • Author(s)
      Sakai R, Ito M, Yoshimoto K, Chikuma S, Kurasawa T, Kondo T, Suzuki K, Takeuchi T, Amano K, Yoshimura A
    • Journal Title

      Clin Transl Immunology

      Volume: 9 Issue: 11

    • DOI

      10.1002/cti2.1203

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kidney GATA3+ regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury.2020

    • Author(s)
      Sakai R, Ito M, Komai K, Iizuka-Koga M, Matsuo K, Nakayama T, Yoshie O, Amano K, Nishimasu H, Nureki O, Kubo M, Yoshimura A.
    • Journal Title

      Cell Mol Immunol.

      Volume: Sep Issue: 5 Pages: 11-11

    • DOI

      10.1038/s41423-020-00547-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD.2020

    • Author(s)
      Imura Y, Ando M, Kondo T, Ito M, Yoshimura A.
    • Journal Title

      JCI Insight.

      Volume: 23;5(14) Issue: 14

    • DOI

      10.1172/jci.insight.136185

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Analysis of the Phenotype of Tregs after Ischemic Stroke, and the Interaction between Treg and Foam Cells2021

    • Author(s)
      伊藤美菜子
    • Organizer
      JCS2021 Secretariat /第85回日本循環器学会学術集会, Web開催
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Analysis of the dynamics of immune cells after stroke.2020

    • Author(s)
      伊藤美菜子
    • Organizer
      第63回日本神経化学会,Web開催
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 脳梗塞後の免疫細胞の動態と炎症抵抗性の解明2020

    • Author(s)
      伊藤美菜子
    • Organizer
      第93回日本生化学会大会,Web開催
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 脳梗塞後の免疫細胞の動態と炎症抵抗性獲得機構の解明2020

    • Author(s)
      伊藤美菜子
    • Organizer
      第20回日本抗加齢医学会総会, 東京
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] The role of Brain regulatory T cells during the chronic phase after CNS injury2019

    • Author(s)
      Minako Ito, Akihiko Yoshimura
    • Organizer
      Brain & Brain Pet 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 中枢神経系疾患における制御性T細胞による組織修復機構の解明2019

    • Author(s)
      伊藤美菜子, 吉村昭彦
    • Organizer
      第40回日本炎症・再生医学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脳内炎症における制御性T細胞の意義の解明2019

    • Author(s)
      伊藤美菜子, 吉村昭彦
    • Organizer
      第84回日本インターフェロン・サイトカイン学会各術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脳内炎症における脳特異的制御性T細胞の分化機構の解明2019

    • Author(s)
      伊藤美菜子, 吉村昭彦
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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