Abstract
OBJECTIVEInvestigation of potential anti‐inflammatory mechanisms of IFN‐ in intestinal epithelial cells (IEC) in models of inflammatory bowel disease (IBD).METHODSGuided by microarray analysis, we utilized qPCR, western blot, and confocal microscopy to characterize epithelial IL‐10 receptor (IL‐10R) expression in vitro. Next, the functional consequences of receptor expression were examined. Finally, IL‐10R expression was investigated in a murine IBD model and in human IBD patient samples.RESULTSIn vitro studies revealed that IFN‐ selectively induced the expression of IL‐10R1 on IEC. Further analysis revealed that IL‐10R1 was expressed predominantly on the apical membrane of polarized IEC. Receptor activation functionally induced canonical IL‐10 target gene expression in IEC, concomitant with enhanced barrier restitution. Colonic tissue isolated from murine colitis revealed that levels of IL‐10R1 and SOCS3 were increased in the epithelium and coincided with increased tissue IFN‐ and IL‐10 cytokines. Immunofluorescent staining revealed apical expression of the IL‐10R in colitic mouse tissue. Finally, diseased human tissue demonstrated increased IL‐10R1 transcript with apical IEC localization.CONCLUSIONSThese results provide novel insight into an anti‐inflammatory role for IFN‐ in intestinal inflammation through the induction of a polarized IL‐10 receptor complex.
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