• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

A study of microbiota activated regulatory B cells in inflammatory bowel diseases.

Research Project

Project/Area Number 17K09382
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionShimane University

Principal Investigator

Mishima Yoshiyuki  島根大学, 学術研究院医学・看護学系, 助教 (30397864)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords腸内細菌 / 炎症性腸疾患 / 制御性免疫細胞 / 粘膜免疫 / Toll like receptor / 制御性B細胞 / IL-10 / Toll like recepter / 5 / 6 / 7 / 8 / 免疫学 / 自然免疫
Outline of Final Research Achievements

Regulatory B cells (Breg) are involved in the pathogenesis of inflammatory bowel diseases. We investigated the molecular mechanisms how resident bacteria induce IL-10-producing Breg and ameliorate mucosal inflammation using several Toll-like receptor (TLR) knockout (KO) mice. B cells from TLR2 KO, but not TLR4 KO or TLR9 KO, mice produced low IL-10 in the presence of bacterial stimulation and failed to ameliorate T cell-mediated colitis. Next, we sought to determine the TLR2-dependent IL-10 production by microbiota-activated B cells. Western blotting indicated that a PI3K-AKT-GSK3B pathway is activated in the presence of TLR2 but not TLR4 stimulation. PI3Kp110d KO B cells were neither produce sufficient IL-10 when stimulated with bacteria nor ameliorated mucosal inflammation in vivo. These findings increase our understanding of the pathogenesis of IBD and regulation of mucosal homeostasis by resident microbiota.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、IBDの病態における腸内細菌を介したBreg誘導機構の一端を解明できたと考える。このシステムを応用し、生体内で効率的にBreg誘導ができるようになれば、安全で有効性のたかい新規のIBD治療法開発につながる可能性がある。難渋している現行のIBD治療とは異なるアプローチであり、実用化されれば臨床的意義は大きいと考える。

Report

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

    (2 results)

All 2019

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10?producing regulatory B cells2019

    • Author(s)
      Mishima Yoshiyuki、Oka Akihiko、Liu Bo、Herzog Jeremy W.、Eun Chang Soo、Fan Ting-Jia、Bulik-Sullivan Emily、Carroll Ian M.、Hansen Jonathan J.、Chen Liang、Wilson Justin E.、Fisher Nancy C.、Ting Jenny P.Y.、Nochi Tomonori、Wahl Angela、Garcia J. Victor、Karp Christopher L.、Sartor R. Balfour
    • Journal Title

      Journal of Clinical Investigation

      Volume: 129 Issue: 9 Pages: 3702-3716

    • DOI

      10.1172/jci93820

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphoinositide 3-Kinase P110δ-Signaling Is Critical for Microbiota-Activated IL-10 Production by B Cells that Regulate Intestinal Inflammation2019

    • Author(s)
      Oka Akihiko、Mishima Yoshiyuki、Liu Bo、Herzog Jeremy W.、Steinbach Erin C.、Kobayashi Taku、Plevy Scott E.、Sartor R. Balfour
    • Journal Title

      Cells

      Volume: 8 Issue: 10 Pages: 1121-1121

    • DOI

      10.3390/cells8101121

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

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi