Impaired mucus clearance exacerbates allergen-induced type 2 airway inflammation in juvenile mice (original) (raw)

Type 2 airway inflammation plays a central role in the pathogenesis of allergen-induced asthma, but the underlying mechanisms remain poorly understood. Recently, we demonstrated that reduced mucociliary clearance, a characteristic feature of asthma, produces spontaneous type 2 airway inflammation in juvenile β-epithelial Na(+) channel (Scnn1b)-transgenic (Tg) mice. We sought to determine the role of impaired mucus clearance in the pathogenesis of allergen-induced type 2 airway inflammation and identify cellular sources of the signature cytokine IL-13. We challenged juvenile Scnn1b-Tg and wild-type mice with Aspergillus fumigatus and house dust mite allergen and compared the effects on airway eosinophilia, type 2 cytokine levels, goblet cell metaplasia, and airway hyperresponsiveness. Furthermore, we determined cellular sources of IL-13 and effects of genetic deletion of the key type 2 signal-transducing molecule signal transducer and activator of transcription 6 (STAT6) and evaluate...