Airway epithelial ATG5 suppresses asthmatic inflammation in mice

Abstract

Objective: To explore the role and mechanisms of airway epithelium-localized ATG5 in asthmatic airway injury and inflammation. Methods: CC10-rtTA/(tetO)7-cre-ATG5(f/f)(atg5(△/△)) mice and atg5(+/+) mice were randomly assigned to control and asthma groups, respectively. Mice of the asthma group were treated with house dust mite extract (HDM), and allergic inflammation, mucus hyperproduction, and markers of autophagy, apoptosis, and necroptosis were examined. Results: Airway epithelium-specific ATG5 deficiency significantly increased the number of BALF total inflammatory cells (171.25±41.50) and eosinophils (114.54±19.61), compared with the control asthma group (42.64±8.72) (P<0.01) and (18.71±7.54) (P<0.01), respectively. Histological analyses showed that airway inflammation deteriorated significantly in atg5(△/△) asthma group (2.00±0.45) compared to atg5(+/+) group (1.23±0.26) (P<0.01). Meanwhile, Th2-related cytokines and mucus production were increased in atg5(△/△) asthma group. These mice displayed enhanced necroptosis markers RIP and RIP3, while the autophagic protein LC3B and apoptotic markers caspase-9 and -3 were not significantly changed. Conclusion: Airway epithelium-localized ATG5 suppresses allergic airway inflammation, likely via modulation of necroptosis, while independent of autophagy and apoptosis.