m6A epitranscriptomic regulation in asthma: mechanisms and therapeutic prospects.

Abstract

Asthma is a heterogeneous airway disease in which chronic inflammation, epithelial barrier injury, immune-cell imbalance and airway remodeling interact to shape variable clinical phenotypes. N6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNA, has emerged as a dynamic epitranscriptomic layer that regulates RNA splicing, export, stability, translation and decay. Recent profiling studies and mechanistic experiments indicate that m6A patterns and m6A regulators are altered in lung tissue, airway epithelial cells, airway smooth muscle cells and immune cells in asthma. These changes influence type 2 inflammation, the balance between T helper 1 (Th1) and T helper 2 (Th2) cells, the balance between T helper 17 (Th17) and regulatory T (Treg) cells, macrophage polarization, epithelial ferroptosis, ciliary function, mitochondrial stress, pollutant responses and structural remodeling. This Review synthesizes current evidence linking m6A writers, erasers and readers to asthma pathobiology, highlights context-dependent and sometimes opposing functions of key regulators such as METTL3, FTO and ALKBH5, and discusses how m6A signatures may inform biomarker discovery and therapeutic development. We also outline major translational barriers, including cell-type specificity, target validation, assay standardization and safety of pharmacologic m6A modulation.