Human IFNε: Spaciotemporal expression, hormone regulation and innate immunity in the female reproductive tract

Interferon epsilon (IFNε) plays an important role in regulating protective immunity in the female reproductive tract in mouse models; but the expression and regulation of this IFNε in the human FRT had not yet been characterised. Here we show that IFNε is selectively and highly expressed in the human FRT, a unique characteristic among the many types of IFN. IFNε has distinct expression patterns in upper compared with lower FRT where it is predominantly expressed in the basal layers of the stratified squamous epithelia. We demonstrate direct regulation of IFNε expression is suppressed by progesterone consistent with its inverse correlation with progesterone receptor expression, but only in the endometrium where its expression therefore fluctuates throughout the menstrual cycle. We show that IFNε regulates immunoregulatory IFN regulated genes (IRGs) in FRT epithelial cells. The characterisation of huIFNε expression in both the upper and the lower FRT epithelia and its protective properties make this IFN well placed to be an important player in mediating hormonal control of FRT immune response and susceptibility to FRT infection. Summary Bourke et al. characterise the novel type I interferon epsilon (IFNε), as the only IFN constitutively expressed throughout the human female reproductive tract (FRT), where it is hormonally regulated and modules IFN dependent FRT immunity.