| Autor: |
Konrad Aden, Ateequr Rehman, Maren Falk-Paulsen, Thomas Secher, Jan Kuiper, Florian Tran, Steffen Pfeuffer, Raheleh Sheibani-Tezerji, Alexandra Breuer, Anne Luzius, Marlene Jentzsch, Robert Häsler, Susanne Billmann-Born, Olga Will, Simone Lipinski, Richa Bharti, Timon Adolph, Juan L. Iovanna, Sarah L. Kempster, Richard S. Blumberg, Stefan Schreiber, Burkhard Becher, Mathias Chamaillard, Arthur Kaser, Philip Rosenstiel |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 16, Iss 8, Pp 2208-2218 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2016.07.054 |
| Popis: |
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 (Il23RΔIEC) have reduced Reg3b expression, show a disturbed colonic microflora with an expansion of flagellated bacteria, and succumb to DSS colitis. Surprisingly, Il23RΔIEC mice show impaired mucosal IL-22 induction in response to IL-23. αThy-1 treatment significantly deteriorates colitis in Il23RΔIEC animals, which can be rescued by IL-22 application. Importantly, exogenous Reg3b administration rescues DSS-treated Il23RΔIEC 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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