Association Between Ferritinophagy and M1 Macrophage Polarization During the Acute Phase of Childhood Allergic Asthma.

BACKGROUND: The pathogenesis of allergic asthma is complex, and the role of macrophage polarization and ferritinophagy in childhood allergic asthma is still unclear. In this study, we preliminarily investigated the polarization status of splenic and lung macrophages during the acute phase of allergic asthma, and further explored the role of ferritinophagy in allergic asthma. METHODS: Detection of three monocyte subpopulations in PBMC of children with acute exacerbations of asthma and healthy children by flow cytometry. Establish an acute-phase model of allergic asthma in young mice sensitized with HDM, evaluate airway inflammation, airway resistance, and airway remodeling. We assessed the polarization status of macrophages in mouse spleen and lung tissues by flow cytometry, RT-PCR. We also detected changes in the ferritinophagy-related indexes, FTH1 and LC3B, with flow cytometry, and changes in co-localization of ferritinophagy-associated proteins in wall-isolated alveolar macrophages by laser confocal microscopy. RESULTS: We found an increase in the proportion of classical monocytes and a decrease in the proportion of non-classical monocytes in the PBMCs of asthmatic children. Therefore, we wanted to verify the changes in monocyte-derived macrophages in a young mouse model. We found that the proportion of splenic and lung macrophages was altered in the HDM-induced mice, which also showed an M1-polarized state. LC3B expression in macrophages increased while FTH1 expression decreased. In addition, we also found NCOA4 and LC3B in alveolar macrophages, FTH1 and LC3B, The co localization of FTH1 and LAMP1 increased, indicating that ferritinophagy was also enhanced. CONCLUSION: Our research results indicate that macrophages in the acute phase model of allergic asthma in young mice exhibit M1 polarization, and an increase in ferritinophagy is associated with the pathogenesis of allergic asthma. These findings establish an associative (not causal) relationship between the two processes, providing new ideas for therapeutic strategies.