The novel type I interferon, interferon epsilon (IFNε) possesses a unique manner of spatiotemporal expression and regulation. Largely studied in the female reproductive tract (FRT), it has been shown to maintain homeostatic conditions and mediate protective immunity against common FRT pathogens. Many FRT pathologies including cancer, endometriosis, and infection can extend detrimentally into the peritoneal cavity, and are characterised by dysregulated immune responses. Therefore, it is hypothesised that IFNε may have protective immunoregulatory effects that influence the phenotype, activity and composition of peritoneal immune cells under both steady state and inflammatory conditions.
Previous research utilizing syngeneic mouse models of high grade serous ovarian cancer (HGSOC) has indicated that IFNε administration alleviates tumour burden and ascites development, accompanied by changes in the activity of peritoneal immune cell populations. Following these observations, the peritoneal immune cells present in both male and female wild-type (WT) and Ifnε-/- mice in steady-state conditions and during inflammation were investigated via immunophenotyping. The results indicated that in homeostatic states, endogenous IFNε maintains a basal immunity in the peritoneal cavity by regulating the peritoneal myeloid cells through their recruitment into the peritoneal cavity, differentiation and proliferation, as well as through the modulation of the activation states in peritoneal lymphoid compartment.
Intraperitoneal administration of exogenous IFNε as a pretreatment prior to the induction of peritonitis in WT mice showed that IFNε may act similarly to IFNβ in the peritoneal cavity during infection, potentially by regulating the migration and activation of the peritoneal immune cells in response to infection. Collectively, these data underline the role of IFNε in maintaining the basal immunity of the murine peritoneal cavity, which may prompt the peritoneal immune response during bacteria-induced inflammation. Thus, IFNε may have potential as a future immunotherapy for peritoneal pathologies that induce aberrant activity in the peritoneal immune cells, primarily peritonitis and HGSOC metastases.