Disruption of intestinal balance can lead to inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Tonic type I IFN production has been implicated in maintaining intestinal homeostasis and IFNAR signalling has protective effects in experimental colitis. We previously showed that IFNε is highly expressed by epithelial cells of FRT, where it is involved in protection against sexually transmitted pathogens. While the expression of IFNε is most abundant in the female reproductive tract (FRT) in mice, expression has also been shown in epithelial cells of jejunum and rectum in rhesus macaques.
We characterised IFNε protein and mRNA expression in human IBD and control colon biopsies and in control and inflamed mouse colon. We then determined whether IFNε plays a role in intestinal inflammation using the DSS colitis model.
Here we show IFNε is expressed in human and mouse intestinal epithelium and that expression is lost in inflamed conditions. Furthermore, IFNε prevents exacerbated intestinal inflammation after DSS treatment, as IFNε-/- mice were highly susceptible with more severe clinical symptoms than wildtype mice. As shown previously for IFNβ, our data indicates IFNε can bind to IFNAR1 in the absence of IFNAR2 and this results in a distinct non-canonical gene signature. Finally, as determined by flow cytometry, the FoxP3+ Treg compartment was decreased in inflamed IFNε-/- colons.
These findings suggest IFNε is a promising therapeutic target for the treatment of IBD.