IFN-ε

Interferon-epsilon (IFN-ε, IFNE) is an atypical type I interferon that, unlike the virus-inducible IFN-α and IFN-β, is expressed constitutively in a hormone-regulated, tissue-restricted manner. IFNE was identified in 2004; its expression is confined primarily to the female reproductive tract-endometrial and cervical epithelium, ovary and oviduct-and is controlled by estrogen and progesterone rather than by pattern-recognition receptor signaling, although it can be further induced by microbial stimuli. IFN-ε engages the canonical IFNAR1/IFNAR2 receptor to activate ISGF3-dependent ISG expression, conferring protection against sexually transmitted pathogens including Chlamydia muridarum, herpes simplex virus type 2 and human immunodeficiency virus in mucosal challenge models. Because IFN-ε maintains baseline mucosal immunity without requiring infection-induced production, it is considered a constitutive sentinel of the reproductive tract; its expression is reduced with menopause and hormonal contraception, correlating with altered mucosal susceptibility to viral infection.