RNA Modifications in T cell Immunity: Mechanisms, Disease Relevance, and Therapeutic Potential

RNA modifications constitute a versatile and dynamic layer of post-transcriptional regulation that enables T lymphocytes to fine-tune gene expression programs in response to developmental, environmental, and pathogenic cues. Chemical marks such as N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), and pseudouridine (Ψ) shape transcript stability, splicing, localization, and translation through coordinated actions of writer, reader, and eraser proteins. Emerging evidence reveals that these pathways orchestrate T cell lineage specification, activation thresholds, effector-memory balance, and immune tolerance, while their dysregulation contributes to infection, autoimmunity, malignancy, and graft rejection. Integrating findings across m⁶A and other epitranscriptomic marks-including m⁵C, Ψ, N⁷-methylguanosine (m⁷G), N¹-methyladenosine (m¹A), N⁴-acetylcytidine (ac⁴C), and N⁶-2'-O-methyladenosine (m⁶A_m) -this review delineates how distinct RNA modifications converge on shared molecular circuits controlling transcriptional, metabolic, and signaling networks in T cell immunity. Aberrant modification patterns reshape cytokine profiles, mitochondrial metabolism, and antigen-driven responses, thereby influencing disease trajectories across diverse pathological contexts. Collectively, these insights establish RNA modification as a central regulatory axis linking transcriptomic plasticity to immune function and therapeutic responsiveness. We further highlight unresolved challenges-such as defining spatiotemporal modification landscapes and achieving selective pharmacological modulation-and propose integrative multi-omics and in vivo perturbation approaches to translate epitranscriptomic mechanisms into targeted immunotherapies.