Autophagy in macrophages modulates the phenotypic switch of asthmatic airway inflammation

<bold>Autophagy in Macrophages Modulates the Phenotypic Switch of Asthmatic Airway Inflammation</bold> <bold>Background:</bold> 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. <bold>Objectives:</bold> This study aims to investigate how autophagy in macrophages modulates the phenotypic switch in asthmatic airway inflammation. <bold>Methods:</bold> Myeloid-specific autophagy-related gene 5 (<italic>Atg5</italic>) knockout mice (LysM-Cre-<italic>Atg5^fl/fl</italic>) and <italic>Atg5^fl/fl</italic> mice were constructed to study the role of macrophage autophagy in asthma, both in vitro and in vivo. <bold>Results:</bold> Autophagy was upregulated in M2 macrophages induced by IL-4, while autophagy flux was blocked in M1 macrophages induced by lipopolysaccharide. LysM-Cre-<italic>Atg5^fl/fl</italic> BMDMs exhibited reduced expression of the M2 marker, <italic>Retnla</italic>, and increased expression of the M1 marker, <italic>Nos2</italic>. Myeloid-specific <italic>Atg5</italic> knockout resulted in a decrease in eosinophils in bronchoalveolar lavage fluid and T_H2 cells in the lungs, along with an increase in neutrophils and T_H17 cells in HDM-induced allergic airway inflammation. <bold>Conclusions:</bold> Myeloid-specific <italic>Atg5</italic> knockout in macrophages induces a switch from eosinophilic to neutrophilic asthmatic airway inflammation by modulating macrophage polarization. <fig><object-id>erj;64/suppl_68/PA4848/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>