| First Author | Aden K | Year | 2016 |
| Journal | Cell Rep | Volume | 16 |
| Issue | 8 | Pages | 2208-2218 |
| PubMed ID | 27524624 | Mgi Jnum | J:236983 |
| Mgi Id | MGI:5810486 | Doi | 10.1016/j.celrep.2016.07.054 |
| Citation | Aden K, et al. (2016) Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation. Cell Rep 16(8):2208-18 |
| abstractText | 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(DeltaIEC)) have reduced Reg3b expression, show a disturbed colonic microflora with an expansion of flagellated bacteria, and succumb to DSS colitis. Surprisingly, Il23R(DeltaIEC) mice show impaired mucosal IL-22 induction in response to IL-23. alphaThy-1 treatment significantly deteriorates colitis in Il23R(DeltaIEC) animals, which can be rescued by IL-22 application. Importantly, exogenous Reg3b administration rescues DSS-treated Il23R(DeltaIEC) 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. |
