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Stress-induced renin causes intestinal inflammation via helper T cells

Research Project

Project/Area Number 20K16280
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Shimba Akihiro  京都大学, 医学研究科, 助教 (30812242)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsレニン / ヘルパーT細胞 / 炎症性腸疾患 / 精神的ストレス / TH17細胞 / 大腸炎
Outline of Research at the Start

精神的ストレスはインターロイキン17産生型ヘルパーT細胞(TH17細胞)の働きを介して炎症性腸疾患を誘引すると考えられているが、その機構は明らかではない。申請者はストレス感知により腎臓から産生されるプロレニンの受容体(PRR)がTH17細胞で発現することに着目し、PRRがTH17細胞の発生を促進すること、ストレスと免疫応答が腸管のTH17細胞を増加させることを見出した。そこで本研究は、PRRがTH17細胞の分化や維持、働きを促進する分子機構と、ストレス時に産生されるプロレニンがTH17細胞を介して炎症性腸疾患の発症と増悪に寄与する可能性を、PRR遺伝子破壊マウスを用いた解析から明らかにする。

Outline of Final Research Achievements

Renin, which controls blood pressure, binds to (pro)renin receptor (PRR). Although hematopoietic cells express PRR, the function of PRR remain unclear. To address this question, we analyzed lymphocyte-specific PRR-deleted mice.
We found that T, B, and innate lymphoid cells were significantly reduced in PRR deficient mice. Furthermore, pro-renin enhanced helper T cell differentiation in vitro. Taken together, these results suggest a possibility that the signals of pro-renin receptor promote the development and maintenance of lymphocyte subsets to cause intestinal inflammation.

Academic Significance and Societal Importance of the Research Achievements

血圧を調整するレニンは細胞膜上の存在するプロレニン受容体に結合するが、受容体を発現する免疫細胞にどのような機能があるか、またシグナルを伝達し得るかこれまで不明であった。本研究から、レニンがアンジオテンシン経路を活性化するだけでなく、リンパ球の恒常性維持に寄与し、1型免疫応答や17型免疫応答を制御することで、癌やウイルスの排除に効果を持つ一方で炎症性腸疾患の誘導に関わる可能性を見出した。これ結果から、血圧調整と免疫系が同時に制御される機構を発見することが期待され、高血圧と同時に起こり得る炎症性疾患発症の理解と治療に貢献する。

Report

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

    (7 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Pleiotropic Effects of Glucocorticoids on the Immune System in Circadian Rhythm and Stress2021

    • Author(s)
      Akihiro Shimba, Aki Ejima, Koichi Ikuta
    • Journal Title

      Front Immunol

      Volume: 706951

    • DOI

      10.3389/fimmu.2021.706951

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immune-enhancing effects of glucocorticoids in response to day-night cycles and stress.2020

    • Author(s)
      Shimba A. and Ikuta K.
    • Journal Title

      Int. Immunol.

      Volume: 32 Issue: 11 Pages: 703-708

    • DOI

      10.1093/intimm/dxaa048

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glucocorticoids regulate circadian rhythm of innate and adaptive immunity.2020

    • Author(s)
      Shimba A. and Ikuta K.
    • Journal Title

      Front. Immunol.

      Volume: 11 Pages: 2143-2143

    • DOI

      10.3389/fimmu.2020.02143

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Control of immunity by glucocorticoids in health and disease.2020

    • Author(s)
      Shimba A. and Ikuta K.
    • Journal Title

      Semin. Immunopathol.

      Volume: 42 Issue: 6 Pages: 669-680

    • DOI

      10.1007/s00281-020-00827-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intestinal epithelial cell-derived IL-15 determines local maintenance and maturation of intra-epithelial lymphocytes in the intestine2019

    • Author(s)
      Zhu Yuanbo、Cui Guangwei、Miyauchi Eiji、Nakanishi Yuki、Mukohira Hisa、Shimba Akihiro、Abe Shinya、Tani-ichi Shizue、Hara Takahiro、Nakase Hiroshi、Chiba Tsutomu、Sehara-Fujisawa Atsuko、Seno Hiroshi、Ohno Hiroshi、Ikuta Koichi
    • Journal Title

      International Immunology

      Volume: 32 Issue: 5 Pages: 307-319

    • DOI

      10.1093/intimm/dxz082

    • NAID

      120006846480

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] ストレスはグルココルチコイドを介してTh17細胞を活性化する2021

    • Author(s)
      榛葉旭恒、生田宏一
    • Organizer
      第30回Kyoto T Cell Conference
    • Related Report
      2021 Annual Research Report
  • [Presentation] Control of T cell immunity by glucocorticoids2021

    • Author(s)
      榛葉旭恒、生田宏一
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Annual Research Report
    • Invited

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Published: 2020-04-28   Modified: 2023-01-30  

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