β ₂ -Adrenoceptor signaling in airway epithelial cells promotes eosinophilic inflammation, mucous metaplasia, and airway contractility

Significance Activation of β 2 -adrenoreceptors (β 2 ARs) on airway smooth muscle cells produces airway relaxation, and β 2 AR agonists are the most widely used bronchodilators for treating asthma. Paradoxically, murine models show β 2 AR activation is also required for expression of cardinal features of the asthma phenotype, including airway hyperresponsiveness (AHR), inflammation, and mucous metaplasia. However β 2 ARs are expressed on all the cell types implicated in the pathogenesis and maintenance of asthma, and which cell type(s) control these asthmatic effects is unknown. Here we show activation of β 2 AR signaling solely on airway epithelium is sufficient to restore/promote the cardinal features of asthma, including inflammation, mucous metaplasia, and AHR. These studies support the role of the airway epithelium as a master regulator of key features of asthma.