After puberty there is a large swing in prevalence with women being two-times more likely than men to have severe asthma.10 However, when women reach menopause the prevalence of asthma equalizes with regard to gender.12 This change in the prevalence of severe asthma strongly suggests a role for sex hormones in asthma pathogenesis.13 Since asthma is a chronic inflammatory disease, it is highly likely that gender differences in airway inflammation influence the gender predilection in asthma. However the mechanisms that regulate the age-related gender differences in asthma prevalence and severity are unknown.
Our laboratory uses multi-disciplinary approaches to determine how sex hormones regulate inflammatory mechanisms important in asthma. To delineate these mechanisms, we isolate PBMCs from the blood of patients with asthma, determine in vitro cell signaling mechanisms involved with T cell differentiation and innate lymphoid cell stimulation, and use mouse models of IL-17A-mediated inflammation and allergic airway inflammation. This multi-pronged approach allows us to determine mechanisms which regulate airway inflammation from many different angles, provides rapid generation of data, and is the foundational research required for the development of new drug targets or strategies for future clinical trials in asthma.
As depicted in the figure below, our current projects target how sex hormones modulate innate and adaptive inflammation associated with asthma, specifically focusing on group 2 innate lymphoid cells (ILCs) and CD4+ Th17 cells.