| First Author | Kominsky DJ | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 3 | Pages | 1267-76 |
| PubMed ID | 24367025 | Mgi Jnum | J:207314 |
| Mgi Id | MGI:5555997 | Doi | 10.4049/jimmunol.1301757 |
| Citation | Kominsky DJ, et al. (2014) IFN-gamma-mediated induction of an apical IL-10 receptor on polarized intestinal epithelia. J Immunol 192(3):1267-76 |
| abstractText | Cytokines secreted at sites of inflammation impact the onset, progression, and resolution of inflammation. In this article, we investigated potential proresolving mechanisms of IFN-gamma in models of inflammatory bowel disease. Guided by initial microarray analysis, in vitro studies revealed that IFN-gamma 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-gamma and IL-10 cytokines. In parallel, studies showed that treatment of mice with rIFN-gamma 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-gamma. |
