Epigenetics and macrophage polarization in asthmatic airway inflammation

Asthma is a highly heterogeneous chronic inflammatory airway disease with a complex pathophysiology involving interactions among genetic, environmental, and immune factors. Macrophages are the most abundant innate immune cells in the lungs, and their polarization states play a central role in the initiation, persistence, and resolution of asthmatic airway inflammation. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA regulation, serve as a critical bridge connecting environmental stimuli to gene expression. They can influence the course of airway inflammation by modulating the function of immune cells such as macrophages. These distinct epigenetic mechanisms intersect and act synergistically, collectively forming an epigenetic regulatory network that governs macrophage polarization during the pathogenesis of asthma. As increasing attention is focused on the role of epigenetics in asthmatic airway inflammation, identifying epigenetic markers that regulate macrophage polarization and targeting the underlying epigenetic mechanisms of this polarization may provide novel therapeutic strategies for specific asthma endotypes. This review systematically elaborates on the epigenetic mechanisms and the phenomenon of macrophage polarization involved in asthmatic airway inflammation. It further untangles the close relationship between epigenetic mechanisms and macrophage polarization, revealing their key roles in asthmatic airway inflammation and providing a new theoretical basis for asthma treatment strategies.