Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation.

ABSTRACT: A plethora of functional and genetic studies have suggested a key role for the IL-23 pathway in chronic intestinal inflammation. Currently, pathogenic actions of IL-23 have been ascribed to specific effects on immune cells. Herein, we unveil a protective role of IL-23R signaling. Mice deficient in IL-23R expression in intestinal epithelial cells (Il23R(?IEC)) have reduced Reg3b expression, show a disturbed colonic microflora with an expansion of flagellated bacteria, and succumb to DSS colitis. Surprisingly, Il23R(?IEC) mice show impaired mucosal IL-22 induction in response to IL-23. ?Thy-1 treatment significantly deteriorates colitis in Il23R(?IEC) animals, which can be rescued by IL-22 application. Importantly, exogenous Reg3b administration rescues DSS-treated Il23R(?IEC) mice by recruiting neutrophils as IL-22-producing cells, thereby restoring mucosal IL-22 levels. The study identifies a critical barrier-protective immune pathway that originates from, and is orchestrated by, IL-23R signaling in intestinal epithelial cells.

SUBMITTER: Aden K 

PROVIDER: S-EPMC5443566 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature