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OTUD3 prevents ulcerative colitis by modulating microbiota-mediated STING activation (part 2)

GSE244077 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/05/12 Platform GPL24247
Summary
Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are suggested to play crucial roles in the pathogenesis of UC. However, the influences of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remain poorly understood. Here, we reveal that OTUD3 suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3’3’-cGAMP) by deubiquitinating stimulator of interferon genes (STING) in the colon. Sting deficiency ameliorated dextran sodium sulfate-induced colitis in Otud3-/- mice. In addition, mice harboring an UC risk missense variant in the Otud3 gene showed pathological features of UC in the colon after transplantation of a fecal microbiome with the potential to produce excessive cGAMP from UC patients. Collectively, these results demonstrate the critical role of OTUD3 in the maintenance of intestinal homeostasis and highlight one mechanism of the interaction between the host (OTUD3 in fibroblasts) and microbiota (STING agonist) in UC development.
Published in
OTUD3 prevents ulcerative colitis by inhibiting microbiota-mediated STING activation
Li B, Sakaguchi T, Tani H et al. · Science immunology 2025 · PMID 40680146 · doi:10.1126/sciimmunol.adm6843
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Also filed as BioProject PRJNA1021204 and SRA study SRP463241. Searching any of these in the dataset finder brings you back here.

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