Poster Presentation Lorne Infection and Immunity 2020

Interferon epsilon regulates lesion establishment and progression in a pre-clinical mouse model of endometriosis (#162)

Fiona L Cousins 1 2 , Eveline D de Geus 3 , Caroline E Gargett 1 2 , Paul J Hertzog 3
  1. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VICTORIA, Australia
  2. Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
  3. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia

Interferon epsilon (IFNε) is a unique immunomodulator that has protective effects in the reproductive tract1. It has been shown to protect against ovarian cancer metastases in a pre-clinical model. Due to the similarities between ovarian cancer and endometriosis (uncontrolled cell proliferation, altered immune cell profiles), we investigated whether IFNε plays a role in endometriosis pathogenesis.

We investigated the contributions of both shedding endometrial tissue and the peritoneal microenvironment to disease pathogenesis using a mouse model of endometriosis2 utilising reciprocal transfer of IFNε-/- donor shedding menstrual tissue to WT oestrogen-primed recipients or WT donor menstrual tissue to IFNε-/- recipients. Lesions were allowed to develop over 3 weeks then analysed for epithelial cell localisation, immune populations and proliferation/cell death markers. Peritoneal exudate cells from recipient mice were also collected and immunophenotyped using flow cytometry.

Lesion volume and lesion area were significantly increased in IFNε-/- recipients and in those WT recipients that has received epsilon depleted menstrual tissue. Lesions from IFNε-/- recipients had more intact glands in comparison to WT recipients, suggesting that IFNε plays a role in lesion progression. Significant differences in immune cell profiles were detected in peritoneal fluid; the activation status of both CD4+ and CD8+ T cell populations was increased (n=5, p<0.05) in the IFNε-/-→WT group and NK cell populations (NKp46+ and NK1.1+ cells n=5, p<0.01) were decreased in IFNε-/- deficient groups.

This data is the first to indicate a role for endogenous IFNε in the establishment and progression of lesions by altering the peritoneal micro-environment and having an effect on lesion morphology. These findings highlight the potential of IFNε as a future therapeutic target for the treatment of endometriosis.

  1. 1. Fung and Mangan et al., 2013. Interferon-ε protects the female reproductive tract from viral and bacterial infection. Science; 339(6123):1088-92. doi: 10.1126/science.1233321.
  2. 2. Greaves, Cousins et al., 2014. A novel mouse model of endometriosis mimics human phenotype and reveals insights into the inflammatory contribution of shed endometrium. AmJPath; 184(7):1930-9. doi: 10.1016/j.ajpath.2014.03.011.