Regulation of m⁶A modifications in Th2-driven allergic responses: impact on responses and therapeutic potential

Th2-driven allergic responses are characterized by allergic reactions and immune dysregulation with complex pathogenesis that warrants urgent in-depth study. The predominant posttranscriptional modification observed in eukaryotic messenger RNAs, N6-methyladenosine (m⁶A), dynamically regulates RNA splicing, which is likely regulated during cell fate determination, cytokine production, and epithelial barrier maintenance in context of Th2-driven allergic responses. This review systematically analyzes the effects of m⁶A modification on the differentiation and functional regulation of major immune cell populations, including dendritic cells, macrophages, T helper cells, B cells, and mast cells, as well as barrier-forming epithelial cells. Additionally, we discuss how m⁶A regulators control the transcription of cytokine-encoding genes, transcription factors that regulate T-cell function, and T lymphocyte activation signals. Furthermore, this paper integrates the latest research advancements and explores the application potential of m⁶A modification for diagnosis and treatment of Th2-driven allergic disorders, including allergic asthma and rhinitis. By presenting a summary of the current progress in this area of research, this paper aims at summarizing the role of m⁶A modification during Th2-driven allergic responses and highlight its therapeutic potential and future research directions.