Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal InflammationReportar como inadecuado

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

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Publication Date: 2016-08-11

Journal Title: Cell Reports

Publisher: Cell/Elsevier

Volume: 16

Issue: 8

Pages: 2208-2218

Language: English

Type: Article

This Version: VoR

Metadata: Show full item record

Citation: Aden, K., Rehman, A., Falk-Paulsen, M., Secher, T., Kuiper, J., Tran, F., Pfeuffer, S., et al. (2016). Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation. Cell Reports, 16 (8), 2208-2218. https://doi.org/10.1016/j.celrep.2016.07.054

Description: This is the final version of the article. It first appeared from Cell/Elsevier via http://dx.doi.org/10.1016/j.celrep.2016.07.054

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 ($\textit{Il23R}^{{\Delta}IEC}$) have reduced Reg3b expression, show a disturbed colonic microflora with an expansion of flagellated bacteria, and succumb to DSS colitis. Surprisingly, $\textit{Il23R}^{{\Delta}IEC}$ mice show impaired mucosal IL-22 induction in response to IL-23. aThy-1 treatment significantly deteriorates colitis in $\textit{Il23R}^{{\Delta}IEC}$ animals, which can be rescued by IL-22 application. Importantly, exogenous Reg3b administration rescues DSS-treated $\textit{Il23R}^{{\Delta}IEC}$ 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.

Sponsorship: This work was supported by DFG Excellence Cluster Inflammation at Interfaces; the SFB877 B9, the SFB 1182 C2 project, and the BMBF IHEC DEEP project TP2.3 and 5.2 (to P.R.); the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007- 2013)/ERC grant agreement 260961 (to A.K.); the National Institute for Health Research Cambridge Biomedical Research Centre, ERC CoG GA 648889, and WTIA 106260-Z-14-Z (to A.K.); NIH DK53056, DK44319, and DK088199 (to R.S.B.); and the Fondation pour la Recherche Medicale (to M.C.).

Embargo Lift Date: 2100-01-01


External DOI: https://doi.org/10.1016/j.celrep.2016.07.054

This record's URL: https://www.repository.cam.ac.uk/handle/1810/260081

Rights: Attribution-NonCommercial-NoDerivatives 4.0 International

Licence URL: http://creativecommons.org/licenses/by-nc-nd/4.0/

Autor: Aden, KonradRehman, AteequrFalk-Paulsen, MarenSecher, ThomasKuiper, JanTran, FlorianPfeuffer, SteffenSheibani-Tezerji, RahelehBreu

Fuente: https://www.repository.cam.ac.uk/handle/1810/260081


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