Epithelial cells that line the conducting airways provide the initial barrier and innate immune responses to the abundant particles, microbes, and allergens that are inhaled throughout life. The transcription factors SPDEF and FOXA3 are both selectively expressed in epithelial cells lining the conducting airways, where they regulate goblet cell differentiation and mucus production. Moreover, these transcription factors are upregulated in chronic lung disorders, including asthma. Here, we show that expression of SPDEF or FOXA3 in airway epithelial cells in neonatal mice caused goblet cell differentiation, spontaneous eosinophilic inflammation, and airway hyperresponsiveness to methacholine. SPDEF expression promoted DC recruitment and activation in association with induction of
Priya Rajavelu, Gang Chen, Yan Xu, Joseph A. Kitzmiller, Thomas R. Korfhagen, Jeffrey A. Whitsett
SPDEF is required for Th2 inflammatory responses, AHR, and recruitment of ST2+ ILCs and IL-4+, IL-13+, and IL-17+ T cells in response to HDM extract in adult mice.
HDM extract (100 μg) was administered i.n. daily for 3 days to adult control and