Epithelially Restricted Interferon Epsilon Protects Against Colitis

Abstract

Background & AimsType I interferon (T1IFN) signalling is crucial for maintaining intestinal homeostasis. We previously found that the novel T1IFN, IFNε, is highly expressed by epithelial cells of the female reproductive tract, where it protects against pathogens. Its function has not been studied in the intestine. We hypothesise IFNε is important in maintaining intestinal homeostasis. MethodsWe characterised IFNε expression in mouse and human intestine by immunostaining and studied its function in the DSS colitis model using both genetic knock-outs and neutralising antibody. ResultsWe demonstrate that IFNε is expressed in human and mouse intestinal epithelium and expression is lost in inflammation. Furthermore, we show IFNε limits intestinal inflammation in mouse models. Regulatory T cell (Treg) frequencies were paradoxically decreased in DSS-treated IFNε-/- mice, suggesting a role for IFNε in maintaining the intestinal Treg compartment. Colitis was ameliorated by transfer of wild-type Tregs into IFNε-/- mice. This demonstrates that IFNε supports intestinal Treg function. ConclusionsOverall, we have shown IFNε expression in intestinal epithelium, and its critical role in gut homeostasis. Given its known role in the female reproductive tract, we now show IFNε has a protective role across multiple mucosal surfaces.