IL-33-mediated mast cell function is female dominant

Abstract

Abstract Allergic asthma is a common chronic disease characterized by airway inflammation and bronchoconstriction. Asthma is more common and more severe in women than in men. One component of allergic inflammation is IL-33, a cytokine released by airway epithelium when these cells are damaged by allergens. Using two models of IL-33-mediated inflammation, we have found that IL-33 elicits a stronger response in female mice than males. These differences are reversed when using castrated mice. Castrated females show reduced IL-33 responses than controls, while castrated males show enhanced responses. IL-33 is a potent mast cell activator in these models. We find that mast cells cultured from female mice respond more strongly to IL-33 than male mast cells. These data support the hypothesis that IL-33-mediated inflammation exhibits female-dominant sexual dimorphism. Further this dimorphism is linked to sex hormones and may be partly explained by IL-33 effects on mast cells.