Grant: Catalyst Grant: Sex as a Variable in Biomedical Research

Asthma is one of the most common health problems in Canada. Many studies have found that adult women are more likely to develop asthma than adult men, but the precise reason for the gender difference in asthma incidence is currently unknown. Asthma is caused by over-production of a group of proteins called type 2 cytokines that induce excessive mucus production and narrowing of airway, which result in breathing difficulty. We have found a family of innate lymphocytes called ILC2 that produces large amounts of type 2 cytokines. We have also found that ILC2 is activated by a protein called IL-33, and female mice have more IL-33 in the lung than male mice of the same age. We think female sex hormones enhance IL-33 production in the lung, which makes lung ILC2 more sensitive to allergens. We will test this idea by comparing the numbers of ILC2 and the amounts of IL-33 in the lung of male and female mice. We will also test the effects of sex hormones on IL-33 production in the lung and allergen-induced ILC2 activation as well as asthma development in mice. Through this study, we hope to find out why adult women are more likely to get asthma than men. This study may result in new ways to treat asthma patients.