Autophagy in macrophages modulates the phenotypic switch of asthmatic airway inflammation

Autophagy in Macrophages Modulates the Phenotypic Switch of Asthmatic Airway Inflammation Background: Macrophages are one of the major immunoregulatory cells during the pathogenesis of asthma. Autophagy is vital for macrophage function, and mutations in autophagy-related genes have been observed in asthma. However, the impact of autophagy in macrophages on asthmatic airways remains unexplored. Objectives: This study aims to investigate how autophagy in macrophages modulates the phenotypic switch in asthmatic airway inflammation. Methods: Myeloid-specific autophagy-related gene 5 (Atg5) knockout mice (LysM-Cre-Atg5fl/fl) and Atg5fl/fl mice were constructed to study the role of macrophage autophagy in asthma, both in vitro and in vivo. Results: Autophagy was upregulated in M2 macrophages induced by IL-4, while autophagy flux was blocked in M1 macrophages induced by lipopolysaccharide. LysM-Cre-Atg5fl/fl BMDMs exhibited reduced expression of the M2 marker, Retnla, and increased expression of the M1 marker, Nos2. Myeloid-specific Atg5 knockout resulted in a decrease in eosinophils in bronchoalveolar lavage fluid and TH2 cells in the lungs, along with an increase in neutrophils and TH17 cells in HDM-induced allergic airway inflammation. Conclusions: Myeloid-specific Atg5 knockout in macrophages induces a switch from eosinophilic to neutrophilic asthmatic airway inflammation by modulating macrophage polarization. erj;64/suppl_68/PA4848/F1 F1 F1