m6A modification in immune-cell inflammatory fate: from RNA fate regulation to therapeutic translation in inflammatory diseases

Abstract

Inflammatory disease is sustained not only by immune activation but also by the failure of activated cells to terminate effector programs and return tissues to homeostasis. This review evaluates N 6 -methyladenosine (m 6 A) as a post-transcriptional regulator of that persistence. Rather than cataloguing diseases or classifying individual m 6 A regulators as pro- or anti-inflammatory, we organize the evidence around a causal chain linking a regulator and target RNA to a site- or reader-dependent change in RNA fate, an immune-cell phenotype, and a disease outcome. Mechanistically developed evidence is concentrated in macrophages and T cells, including STAT1 stability and decay, SOCS turnover, SLC37A2 translation, and lineage-specific T-cell programs. Mechanisms in other innate and adaptive immune populations are emerging, but cell-subset resolution and disease-stage validation remain uneven. Across inflammatory signaling, immunometabolic, and cell-death pathways, the same m 6 A regulator can produce opposing outcomes through different target transcripts or readers. We therefore distinguish mechanistically resolved, functional/intermediate, and associative evidence while highlighting the limitations of global m 6 A assays, bulk-tissue profiling, and pathway-level inference. The translational value of m 6 A is likely to depend on target-RNA selection, cell-specific delivery, disease-stage timing, and preservation of protective immunity and tissue repair. An evidence-aware, transcript-centered framework may help move m 6 A research from descriptive association toward causal immune-state biology and clinically testable interventions.