Wood smoke fire particulate matter induces eosinophilic asthma in a Sprouty2-dependent manner in mice

Wood smoke particulate matter (WSP) is an important public health hazard. The objective of this study was to establish a mouse model of WSP-induced airway inflammation and hyperreactivity. WSP has been linked to a genetic risk variant that regulates the expression of the ERK1/2 regulator Sprouty2 (Spry2). We examined the importance of Spry2 in WSP-induced airway pathology and activation of critical immune cells in mice with inducible Spry2 gene deletion. A short-term airway exposure of naïve B6 mice to WSP induced airway hyperreactivity to methacholine and eosinophilic, and, to a lower extent, modest neutrophilic inflammation, mucus production and airway remodeling. The induction of the foregoing pathologic abnormalities was associated with number of ILC2s and CD4 T cells, increased ERK1/2 phosphorylation, and increased production of IL5, IL13 and IL17A. Inducible deletion of Spry2 prevented the induction airway hyperreactivity, airway inflammation, mucus production, Collagen deposition, and phosphorylation of ERK1/2. Spry2-/- inhibited the increase in ILC2 but not CD4 T cell frequency. ERK1/2 phosphorylation was inhibited in both ILC2s and Th2 cells in the absence of Spry2. Spry2 deletion reduced IL5, IL13 and IL17A expressing ILC2s. Similarly, Spry2 deletion reduced production of IL17A and IL13 but not IL5 in CD4 T cells. We conclude that WSP induces eosinophilic and modestly neutrophilic airway inflammation and other features of asthma. Spry2 plays a non-redundant role in WSP-induced airway pathologies, in part, by facilitating ERK1/2 activation.