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Analysis of homeostatic mechanisms of intestinal bacteria with a focus on IL-5-producing cells

Research Project

Project/Area Number 21K05466
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionToyama Prefectural Institute for Pharmaceutical Research

Principal Investigator

Tsutomu Yanagibashi  富山県薬事総合研究開発センター, その他部局等, 主任研究員 (60710887)

Co-Investigator(Kenkyū-buntansha) 山崎 輝美 (長井輝美)  金沢大学, ナノ生命科学研究所, 特任助教 (20558134)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsIL-5 / 腸内細菌 / IL-33
Outline of Research at the Start

腸内細菌の構成バランスの破綻は,炎症,代謝,神経疾患等の発症原因となるため,これら疾病の予防や治療では,腸内細菌バランスを正常な状態に保つことが重要となる。研究代表者らは,大腸に存在する2型自然リンパ球(ILC2)がインターロイキン(IL)-5を恒常的に産生し,腸内細菌構成バランスの適正化に関連することを見出している。本研究では,定常状態における大腸ILC2のIL-5産生調節機構を解明し,ILC2を中心した腸管恒常性維持の全体像の理解を目指す。

Outline of Final Research Achievements

ILC2 produces IL-5 at steady state in the colon and contributes to the proper compositional balance of the intestinal microbiota. However, the regulatory mechanism of IL-5 production by ILC2 at steady state remains elusive. In this study, using IL-33-deficient mice, we demonstrated that IL-33 is essential for the maintenance of IL-5 production by ILC2. Furthermore, IL-5 production by ILC2 was altered in response to changes in the gut microbiota caused by antibiotic treatment, suggesting that gut bacteria regulate IL-5 production by ILC2. Notably, IL-33 production was not altered by antibiotic treatment. These findings suggest that IL-33 and gut bacteria independently contribute to IL-5 production by ILC2 through distinct pathways.

Academic Significance and Societal Importance of the Research Achievements

本研究では、定常状態における大腸ILC2のIL-5産生調節機構の解明に取り組み、大腸IL-33と腸内細菌がそれぞれ独立した経路でILC2のIL-5産生に寄与することを明らかにした。研究代表者らは、大腸ILC2がIL-5依存的に腸内細菌の構成バランスを適正化し、腸内細菌の恒常性維持において重要な役割を果たすと考えている。一方で、ILC2はIL-5過剰産生によってアレルギー反応や肺動脈高血圧症の発症にも寄与することから、その制御が健康維持に重要であると考えられる。本研究で得られた知見は、ILC2のIL-5産生を調節する薬剤や食品の開発に資するものであり、社会実装への応用が期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Remarks (1 results)

  • [Journal Article] Impact of Vancomycin Treatment and Gut Microbiota on Bile Acid Metabolism and the Development of Non-Alcoholic Steatohepatitis in Mice2023

    • Author(s)
      Kasai Kaichi、Igarashi Naoya、Tada Yuki、Kani Koudai、Takano Shun、Yanagibashi Tsutomu、Usui-Kawanishi Fumitake、Fujisaka Shiho、Watanabe Shiro、Ichimura-Shimizu Mayuko、Takatsu Kiyoshi、Tobe Kazuyuki、Tsuneyama Koichi、Furusawa Yukihiro、Nagai Yoshinori
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 4 Pages: 4050-4050

    • DOI

      10.3390/ijms24044050

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Betulin Attenuates TGF-β1- and PGE<sub>2</sub>-Mediated Inhibition of NK Cell Activity to Suppress Tumor Progression and Metastasis in Mice2022

    • Author(s)
      Ogasawara Masaru、Yamasaki-Yashiki Shino、Hamada Masahiro、Yamaguchi-Miyamoto Tomomi、Kawasuji Toru、Honda Hiroe、Yanagibashi Tsutomu、Ikutani Masashi、Watanabe Yasuharu、Fujimoto Ryota、Matsunaga Takayuki、Nakajima Noriyuki、Nagai Yoshinori、Takatsu Kiyoshi
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 45 Issue: 3 Pages: 339-353

    • DOI

      10.1248/bpb.b21-00921

    • NAID

      130008165815

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2022-03-01
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of Macrophages in Advanced Liver Fibrosis, Identified Using a Newly Established Mouse Model of Diet-Induced Non-Alcoholic Steatohepatitis2022

    • Author(s)
      Tada Yuki、Kasai Kaichi、Makiuchi Nana、Igarashi Naoya、Kani Koudai、Takano Shun、Honda Hiroe、Yanagibashi Tsutomu、Watanabe Yasuharu、Usui-Kawanishi Fumitake、Furusawa Yukihiro、Ichimura-Shimizu Mayuko、Tabuchi Yoshiaki、Takatsu Kiyoshi、Tsuneyama Koichi、Nagai Yoshinori
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 21 Pages: 13251-13251

    • DOI

      10.3390/ijms232113251

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Remarks] 富山県薬事総合研究開発センター

    • URL

      https://www.pref.toyama.jp/1285/kurashi/kenkou/iryou/1285/index.html

    • Related Report
      2022 Research-status Report 2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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