GSE208325
USP2 promotes experimental colitis and bacterial infections by inhibiting the proliferation of myeloid cells and remodeling the extracellular matrix network
Inflammatory bowel disease (IBD) is closely associated with dysregulation of genetic factors and microbial environment. Here, we report a susceptible role of ubiquitin-specific protease 2 (USP2) in experimental colitis and bacterial infections. USP2 is upregulated in the inflamed mucosa of IBD patients and in the colon of mice treated with dextran sulfate sodium salt (DSS). Knockout or pharmacologic inhibition of USP2 promotes the proliferation of myeloid cells to activate IL-22 and IFNg production of T cells. In addition, knockout of USP2 in myeloid cells inhibits the production of pro-inflammatory cytokines to relieve the dysregulation of extracellular matrix (ECM) network and promote the gut epithelial integrity after DSS treatment. Consistently, Lyz2-Cre;Usp2fl/fl mice exhibit hyper-resistance to DSS-induced colitis and Citrobacter rodentium infections compared to Usp2fl/fl mice. These findings highlight an indispensable role of USP2 in myeloid cells to modulate T cell activation and epithelial ECM network and repair, indicating USP2 as a potential target for therapeutic intervention of IBD and bacterial infections in the gastrointestinal system. Overall design: Comparative gene expression profiling analysis of RNA-seq data for Usp2 sufficient myeloid cells and Usp2 defficient myeloid cells from lamina propria of mice with DSS-induced colitis.