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

Aden, K., Rehman, A., Falk-Paulsen, M., Secher, T., Kuiper, J., Tran, F., Pfeuffer, S., Sheibani-Tezerji, R., Breuer, A., Luzius, A., Jentzsch, M., Hasler, R., Billmann-Born, S., Will, O., Lipinski, S., Bharti, R., Adolph, T., Iovanna, J. L., Kempster, S. L., Blumberg, R. S., Schreiber, Stefan, Becher, B., Chamaillard, M., Kaser, A. and Rosenstiel, Philip (2016) Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation. Cell Reports, 16 (8). pp. 2208-2218. DOI doi.10.1016/j.celrep.2016.07.054.

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Supplementary data:


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.

Document Type: Article
Additional Information: Times Cited: 0 Aden, Konrad Rehman, Ateequr Falk-Paulsen, Maren Secher, Thomas Kuiper, Jan Tran, Florian Pfeuffer, Steffen Sheibani-Tezerji, Raheleh Breuer, Alexandra Luzius, Anne Jentzsch, Marlene Haesler, Robert Billmann-Born, Susanne Will, Olga Lipinski, Simone Bharti, Richa Adolph, Timon Iovanna, Juan L. Kempster, Sarah L. Blumberg, Richard S. Schreiber, Stefan Becher, Burkhard Chamaillard, Mathias Kaser, Arthur Rosenstiel, Philip
Research affiliation: Kiel University
Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Refereed: Yes
Open Access Journal?: No
DOI etc.: doi.10.1016/j.celrep.2016.07.054
ISSN: 2211-1247
Projects: Future Ocean
Date Deposited: 27 Feb 2017 09:34
Last Modified: 24 Sep 2019 00:11
URI: http://oceanrep.geomar.de/id/eprint/35988

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