Estrogen Receptor-α signaling increases allergen-induced airway inflammation in obese mice 3014

Abstract Description Asthma prevalence and severity is increased in obese women compared to lean women and men. Our prior research showed that ovarian hormones increased Th2- and Th17-mediated airway inflammation in lean female mice and that estrogen signaling through estrogen receptor-α (ERα/Esr1) increased Th17 differentiation and airway inflammation. Therefore, we hypothesize that ovarian hormones increase Th2 and Th17-mediated airway inflammation in high fat diet (HFD) mice. Sham-operated (S.O.) and ovariectomized (OVX) female mice were placed on control or HFD for 8 weeks followed by house dust mite (HDM) intranasal sensitization and challenge. BAL fluid and lungs were harvested 24 hours after the last HDM challenge to assess for inflammation. OVX female mice on HFD had decreased infiltration of eosinophils and neutrophils, decreased lung Th2 and Th17 cells, and decreased circulating IgE expression compared to the S.O. mice on HFD and S.O. or OVX mice on control chow. Using the same HFD–HDM protocol, a similar experiment was conducted using Esr1fl/fl CD4cre+ and Esr1fl/fl female and male mice. HFD-HDM Esr1fl/fl CD4cre+ female mice had decreased eosinophils and neutrophils in BAL fluid and decreased lung Th2 and Th17 cells compared to HFD–HDM Esr1fl/fl female mice. Combined our data show that ER- α signaling in CD4 T cells increases Th17-mediated airway inflammation in HFD mice and provide a potential mechanism for increased asthma prevalence in obese women compared to lean women. Funding Sources T32 GM139800 T32 AI138932 Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)