Female specific mechanisms of house dust mite induced airway hyperreactivity

In adults, asthma incidence is significantly higher in females, and they develop a more severe form of asthma than males. Airway hyperreactivity (AHR) is one of the main symptoms of allergic asthma. Mouse models of allergic inflammation show that female mice have greater airway inflammation and greater airway hyperreactivity (AHR). Females have more TH2 inflammatory cells during allergic inflammation. AHR is the second defining feature of asthma and causes excessive bronchospasm, secretions, and cough in response to even small amounts of inflammation or irritants. The mainstay of asthma therapy is inhaled corticosteroids which significantly lower TH2 inflammation but have minimal effect on AHR. Steroids also do not provide adequate relief in females and fail to prevent or reverse AHR in animal models of allergic asthma despite eliminating eosinophilia. Targeting TH2-associated cytokines also fails to reduce clinical AHR. Airway sensory afferents have been shown to be critical in AHR in both male and female mice, but the mechanisms of AHR in females remain elusive. We observed that house dust mite (HDM) induced AHR was higher in female mice compared to males. Additionally, the HDM-induced airway inflammation was higher in females compared to males. The levels of circulating prolactin in females suffering from asthma are higher than males. Studies have shown that PRLR expressed on sensory neurons is essential for the development of inflammatory pain and migraine in females. Thus, we hypothesized that prolactin signaling is essential for the development of AHR in females. We observed a significantly higherrelease of CGRP, a neuropeptide released after nerve terminal activation, from the airways of donated human female airway explants. We observed a significantly higher release of CGRP from the airways of donated human asthmatic female airway explants as compared to males. We performed qPCR of PRLR in the airways of donated human female and mice airways and found significantly higher expression of PRLR as compared to males. Our data suggests that PRLR signaling is important in mediating allergic AHR. Warren Alpert foundation grant This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.