1. Academic Validation
  2. IFN-γ-mediated induction of an apical IL-10 receptor on polarized intestinal epithelia

IFN-γ-mediated induction of an apical IL-10 receptor on polarized intestinal epithelia

  • J Immunol. 2014 Feb 1;192(3):1267-76. doi: 10.4049/jimmunol.1301757.
Douglas J Kominsky 1 Eric L Campbell Stefan F Ehrentraut Kelly E Wilson Caleb J Kelly Louise E Glover Colm B Collins Amanda J Bayless Bejan Saeedi Evgenia Dobrinskikh Brittelle E Bowers Christopher F MacManus Werner Müller Sean P Colgan Dunja Bruder
Affiliations

Affiliation

  • 1 Department of Anesthesiology and Perioperative Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045;
Abstract

Cytokines secreted at sites of inflammation impact the onset, progression, and resolution of inflammation. In this article, we investigated potential proresolving mechanisms of IFN-γ in models of inflammatory bowel disease. Guided by initial microarray analysis, in vitro studies revealed that IFN-γ selectively induced the expression of IL-10R1 on intestinal epithelia. Further analysis revealed that IL-10R1 was expressed predominantly on the apical membrane of polarized epithelial cells. Receptor activation functionally induced canonical IL-10 target gene expression in epithelia, concomitant with enhanced barrier restitution. Furthermore, knockdown of IL-10R1 in intestinal epithelial cells results in impaired barrier function in vitro. Colonic tissue isolated from murine colitis revealed that levels of IL-10R1 and suppressor of cytokine signaling 3 were increased in the epithelium and coincided with increased tissue IFN-γ and IL-10 cytokines. In parallel, studies showed that treatment of mice with rIFN-γ was sufficient to drive expression of IL-10R1 in the colonic epithelium. Studies of dextran sodium sulfate colitis in intestinal epithelial-specific IL-10R1-null mice revealed a remarkable increase in disease susceptibility associated with increased intestinal permeability. Together, these results provide novel insight into the crucial and underappreciated role of epithelial IL-10 signaling in the maintenance and restitution of epithelial barrier and of the temporal regulation of these pathways by IFN-γ.

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