In the female reproductive tract (FRT), homeostasis is maintained to enable embryo implantation and development in parallel with priming of the immune system, which protects against localised infection. The FRT is at risk from mucosal pathogens including sexually transmitted infections (STIs) and women in the progesterone-regulated stage of cycle are more susceptible to STIs. Type I Interferons (IFNs) including the novel IFN epsilon (ɛ) are important innate cytokines in the immune response against STIs.  Intriguingly for a type I IFN, the expression of IFNɛ is localised in the FRT, most notably in uterine epithelial cells (UEC). We have previously demonstrated that this novel cytokine protects mice from experimental models of STIs – Chlamydia muridarum and Herpes Simplex virus. We are currently assessing the role of IFNɛ in patient samples.

Epithelial cells are the first line of defense against FRT infections, forming a mucosal barrier as well as producing many cytokines and chemokines to provide a mucosal immune response, however, orchestration of this response remains poorly understood. We demonstrate here the differential responsiveness of uterine epithelial cells (UEC) to pathogen stimulation depending on the stage of cycle, which offers a unique insight in to the role of the innate immune response in the hormone-regulated environment of the FRT.

Levels of IFNɛ also differ with the hormone-regulated stages of the menstrual cycle and are significantly reduced at the progestin-regulated and infection-sensitive stage of cycle. Importantly, in UEC from women at different stages of cycle, and in particular at the window of vulnerability for infections, recombinant IFNɛ is effective in inducing anti-pathogen IFN response genes including ISG15 and OAS. Thus, investigation of the role of IFNɛ in the FRT may identify new therapeutic strategies for manipulating the innate immune response in infection, through regulation of the endogenous control mechanisms.