Epitranscriptomic regulation of immunity: The role of m6A in shaping immune response dynamics.

Abstract

N6-methyladenosine (m6A) is the most prevalent internal modification found in eukaryotic mRNAs and plays a critical role in shaping immune response. It acts as a dynamic regulatory step modulating the splicing, stability, degradation and translation of target mRNAs involved in regulating immune outcome. These effects are mediated by the dynamic interplay of m6A methyltransferases ("writers"), demethylases ("erasers"), and binding proteins ("readers") which work in concert to fine-tune immune activation and suppression. m6A modifications modulate both innate and adaptive immune responses by regulating chemokine signaling, inflammation, and guiding the lineage commitment and function of various cells involved in immune regulation. For example, m6A-modified mRNAs encoding interferons and pro-inflammatory cytokines are translated more efficiently, facilitating a swift response to infection, while m6A-mediated degradation of pro-inflammatory transcripts offers a counterbalance, allowing immune cells to fine-tune responses and limit overactivation. In T cells, m6A readers influence antigen responsiveness and immune tolerance, while in regulatory T cells, m6A plays a key role in maintaining immune equilibrium. In this review, we present an in-depth overview of how m6A methylation shapes immune function and outline its potential as a therapeutic target. A detailed understanding of the interplay between m6A and immune regulation may provide valuable insights for developing novel therapies for immune-related diseases.