Protecting mucosal surfaces from infection requires coordinated molecular and cellular responses aligned with physiological changes such as cell morphology, proliferation, programmed death, and with innate and adaptive immune responses tolerant to commensals but responsive to pathogens. Cytokines such as IFNs are crucial mediators of such responses. Classic type I IFNs, the 14 a subtypes and b, and the type III IFN l are induced by pathogens, produced transiently to control their efficacy:toxicity; but are distinguished by specific type I and III receptors that are respectively ubiquitous or cell specific especially to epithelial cells. By comparison the unique type I IFNe is constitutively expressed by epithelial cells at low levels and has unique properties commensurate with spatiotemporal nature of its expression1. We have shown using knock-out mice and neutralizing antibodies, etc that IFNe is critical for optimal responses to viral infections HSV, HIV, Zika and bacterial infection , chlamydia 2-4. IFNe can directly induce antiviral molecules in cells, and can also control immune responses. We have shown in these different models that IFNe regulates CD8 T cells, Treg or NK cells5. We have also shown that these molecular and cellular responses to IFNe equip it as a potent suppressor of tumours in the female reproductive tract6. The challenges are to dissect how we can utilize these unique properties of IFNe for clinical benefit.