Work

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

Year: 2026

Type: article

Abstract: 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. Plain Language Summary: What is the context? Allergic asthma is a common respiratory disease in children. The exact mechanisms that trigger an acute asthma attack are not fully understood. Immune cells called macrophages play an important role in lung inflammation. A cellular process called “ferritinophagy”, which involves the recycling of iron, might also be involved in this process. What did the study investigate? This study aimed to investigate two key questions during the acute phase of childhood allergic asthma: Do macrophages shift towards a pro-inflammatory state (known as M1 polarization)? Is the ferritinophagy process activated in these macrophages? What did the researchers do? We first analyzed immune cells in the blood of children with asthma. Then, we established a house dust mite-induced allergic asthma model in young mice to mimic the human disease. We assessed airway inflammation and examined the polarization status of macrophages in the spleen and lungs of these mice. We also measured key indicators of ferritinophagy. What were the main findings? Children with asthma had a higher proportion of pro-inflammatory monocytes (precursors to macrophages) in their blood. Mice with asthma showed significant lung inflammation and airway hypersensitivity. Macrophages in the asthmatic mice were predominantly polarized to the pro-inflammatory M1 type in both the spleen and lungs. The ferritinophagy process was significantly enhanced in these macrophages, indicating dysregulated iron metabolism. What do the findings mean? Our findings indicate that both M1 macrophage polarization and enhanced ferritinophagy are key features of acute allergic asthma in children. These two processes are likely interconnected and contribute to the worsening of inflammation. Targeting either macrophage polarization or ferritinophagy could offer new therapeutic strategies for treating allergic asthma. Keywords: childhood allergic asthma, HDM, macrophage polarization, ferritinophagy, LC3B, FTH1

Source: Journal of Inflammation Research

DOI: 10.2147/jir.s569956

Authors: Jingjing Li, Xing Wang, Xiaofeng Shi, Yelin Jiang, Ren Shen

Institution: Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

Language: English

Topic: Asthma and respiratory diseases

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836