期刊
CELL REPORTS
卷 16, 期 8, 页码 2208-2218出版社
CELL PRESS
DOI: 10.1016/j.celrep.2016.07.054
关键词
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类别
资金
- DFG Excellence Cluster Inflammation at Interfaces
- BMBF IHEC DEEP project [TP2.3, 5.2]
- European Research Council under the European Community's Seventh Framework Programme (FP7)/ERC [260961]
- National Institute for Health Research Cambridge Biomedical Research Centre [ERC CoG GA 648889, WTIA 106260-Z-14-Z]
- NIH [DK53056, DK44319, DK088199]
- Fondation pour la Recherche Medicale
- [SFB877 B9]
- [SFB 1182 C2]
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 (II23R(Delta IEC)) have reduced Reg3b expression, show a disturbed colonic microflora with an expansion of flagellated bacteria, and succumb to DSS colitis. Surprisingly, Il23R(Delta IEC) mice show impaired mucosal IL-22 induction in response to IL-23. alpha Thy-1 treatment significantly deteriorates colitis in Il23R(Delta IEC) animals, which can be rescued by IL-22 application. Importantly, exogenous Reg3b administration rescues DSS-treated Il23R(Delta 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.
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