Bronchial pyroptosis promotes Th17 inflammation in a steroid-insensitive toluene diisocyanate-induced asthma model

Abstract <bold>Background:</bold> Bronchial cell pyroptosis and IL-17 respectively participates in the pathogenesis of steroid-insensitive asthma. In this study, we aim to explore the relation between bronchial cell pyroptosis and Th17 in airway inflammation of steroid-insensitive asthma. <bold>Methods:</bold> The steroid-insensitive asthma mice model was induced by toluene diisocyanate (TDI), which were also induced with NLPR3 (NOD-, LRR- and pyrin domain-containing protein 3) inhibitor. The bronchial cell pyroptosis was observed by transmission electron microscope, and pyroptosis cytokines (pro-caspase-1、caspase-1 p20、pro-GSDMD、cleaved-GSDMD) were assessed by western blotting. Th17 in airway was identified by flow cytometry. IL-17A, IL-17F and STAT3 proteins were evaluated using western blotting. <bold>Results:</bold> In steroid-insensitive asthma mice, the morphology of bronchial cell pyroptosis was confirmed under transmission electron microscope. Compared with controls, caspase-1 p20 and cleaved-GSDMD protein levels were significantly increased in steroid-insensitive asthma mice, which could be reversed by NLPR3 inhibitor. Th17 cells and proteins of IL-17A, IL-17F and STAT3 were also increased in airway of steroid-insensitive asthma mice, which also could be reversed by NLPR3 inhibitor. <fig><object-id>erj;64/suppl_68/PA4850/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <bold>Conclusion:</bold> Bronchial pyroptosis promotes Th17 inflammation in airway of steroid-insensitive TDI-induced asthma model.