Serum exosomes derived from Hp-positive gastritis patients inhibit MCP-1 and MIP-1α expression via NLRP12-Notch signaling pathway in intestinal epithelial cells and improve DSS-induced colitis in mice

Epidemiological and basic research has suggested that Helicobacter pylori (H. pylori, Hp) infection has a protective function in inflammatory bowel disease (IBD); however, the mechanisms are not very clear. Here, we investigated the role of exosomes derived from Hp-infected patients in IBD. Human intestinal epithelial cells were treated with serum exosomes derived from Hp-positive chronic gastritis patients (Exo(Hp)), the expression of cytokines, inflammasome and signal pathway genes were detected by antibody microarray or PCR array. Furthermore, DSS-induced colitis mice were treated with exosomes by intraperitoneally injection. The results demonstrated that Exo(Hp) promoted NLRP12 expression in intestinal epithelial cells, and NLRP12 decreased chemokine MCP-1 and MIP-1α expression by inhibiting the Notch signaling pathway. Next, in vivo, results showed that Exo(Hp) attenuated the inflammatory responses in DSS-induced colitis mice and improved colitis symptoms, outcomes associated with an increase in NLRP12 expression. Furthermore, the immunohistochemistry results showed that NLRP12 was negatively correlated with the disease activity of pediatric IBD patients. These results provide new theoretical bases for further elucidation of the protective mechanisms of Hp infection in IBD, and suggest new targets for explorations of effective interventional strategies for IBD.