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2022 Fiscal Year Annual Research Report

Maintenance of intestinal homeostasis by deubiquitinase PTUD3

Research Project

Project/Area Number 21F21112
Research InstitutionOsaka University

Principal Investigator

竹田 潔  大阪大学, 大学院医学系研究科, 教授 (20309446)

Co-Investigator(Kenkyū-buntansha) LI BO  大阪大学, 医学(系)研究科(研究院), 外国人特別研究員
Project Period (FY) 2021-04-28 – 2023-03-31
Keywordsintestine stromal cell / ubiquitination
Outline of Annual Research Achievements

To assess the physiological function of OTUD3 in the intestine, we generated Otud3 deficient mice by using gene targeting. We observed that deficient mice exhibited more severe colitis during DSS administration.In murine colon, Otud3 mRNA was highly expressed in fibroblasts relative to epithelia cells and innate and adaptive immune cells. Otud3 deficiency in fibroblasts leads to aggravation of colitis.By performing scRNA-seq analysis using colonic fibroblasts, we found
OTUD3 modulates the STING-IFN signaling pathway in a special subset of colonic fibroblasts.By making use of antibiotics (ABX) treatment and germ free mice, we found OTUD3 modulates the microbial cGAMP-STING-IFN pathway in colonic fibroblasts.We generated a knock-in strain of OTUD3 UC risk variant mice, and confirmed this UC risk variant in OTUD3 is associated with dysregulation of STING activation in intestinal fibroblasts.
Now I am preparing to submit the paper to a major acdemic journal.Fibroblasts, the most abundant structural cells, exert homeostatic functions but also drive disease pathogenesis. Single-cell technologies have illuminated the shared characteristics of pathogenic fibroblasts in multiple diseases. However, the molecular mechanisms underlying the disease-associated fibroblast phenotypes remain largely unclear. Our findings provide a mechanistic basis for pathogenic fibroblast polarization and have important therapeutic implications

Research Progress Status

令和4年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和4年度が最終年度であるため、記入しない。

  • Research Products

    (2 results)

All 2022

All Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Deubiquitinase OTUD3 prevents colitis by modulating microbiota-dependent STING activation in PDGFRα+ stromal cells2022

    • Author(s)
      Bo Li
    • Organizer
      The 20th Awaji International Forum on Infection and Immunity
    • Int'l Joint Research
  • [Presentation] Deubiquitinase OTUD3 prevents colitis by modulating microbiota-dependent STING activation in PDGFRα+ stromal cells2022

    • Author(s)
      Haruka Tani
    • Organizer
      the 51st Annual Meeting of the Japanese Society for Immunology

URL: 

Published: 2023-12-25  

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