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Ovarian Hormones Increase Alternaria Extract Induced ILC2 Activation
Sunday, March 6, 2016: 2:30 PM
Room 406AB (Convention Center)
Dawn C. Newcomb, Ph.D., , , , , , ,
Rationale: Women have an increased prevalence of asthma compared to men, suggesting a role for sex hormones in asthma pathogenesis. Alternaria alternata extract (Alt Ext), a fungal aeroallergen associated with severe asthma exacerbations, increased group 2 innate lymphoid cells (ILC2) production of IL-5 and IL-13 which are central for the asthma phenotype. However, the role of sex hormones on ILC2 cytokine expression and innate immune-mediated airway inflammation remains unknown. We hypothesize that ovarian hormones increase Alt Ext-induced ILC2 cytokine expression and innate immune-mediated airway inflammation. 

Methods: Four week old female and male BALB/c mice underwent gonadectomy, reducing ovarian hormones or testosterone, or a sham surgery. When mice were 6-8 weeks old, Alt Ext was administered intranasally for 4 consecutive days, and lungs and bronchoalveolar lavage (BAL) fluid were harvested on day 5. Protein expression of IL-5, IL-13, and IL-33, a cytokine known to activate ILC2 cytokine expression, and infiltration of inflammatory cells was determined in BAL fluid. IL-5+ lung ILC2 were determined by flow cytometry.  

Results: Sham operated female mice had significantly increased IL-5, IL-13, and IL-33 protein expression in BAL fluid and IL-5+ lung ILC2 compared to gonadectomized female mice, male mice and sham operated male mice (n=8 mice per group, p<0.05). Further, infiltration of eosinophils and lymphocytes was increased in sham-operated female mice compared to gonadectomized female mice, male mice and sham operated male mice. 

Conclusions: Ovarian hormones significantly increased Alt Ext-induced lung ILC2 cytokine expression and provide a potential mechanism for increased asthma prevalence in women compared to men.