Although published studies have demonstrated that interferon epsilon (IFNε) has a crucial role in regulating protective immunity in the mouse female reproductive tract (mFRT), expression and regulation of IFNε in the human female reproductive tract (hFRT) have not been characterised. To characterise human IFNε, we obtained hFRT samples from a well- characterized cohort of women, enabling us to comprehensively assess ex vivo IFNε expression in the hFRT at various stages of the menstrual cycle. We found that among the various types of IFNs, IFNε is uniquely selectively and constitutively expressed in the hFRT epithelium. It has distinct expression patterns in the surface and glandular epithelia of the upper hFRT compared with basal layers of the stratified squamous epithelia of the lower hFRT. There is cyclical variation of IFNε expression in the endometrial epithelium of the upper hFRT and not in the distal FRT, consistent with selective endometrial expression of the progesterone receptor and regulation of the IFNE promoter by progesterone. Since we show IFNε stimulates important protective IFN-regulated genes (IRGs) in FRT epithelium, this characterisation is a key element in understanding the mechanisms of hormonal control of mucosal immunity.
Nollaig M. Bourke, Sharon L. Achilles, Stephanie U-Shane Huang, Helen E. Cumming, San S. Lim, Irene Papageorgiou, Linden J. Gearing, Ross Chapman, Suruchi Thakore, Niamh E. Mangan, Sam Mesiano, Paul J. Hertzog