Work

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

Year: 2025

Type: article

Abstract: 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 N 6 -methyladenosine (m 6 A), 5-methylcytosine (m 5 C), 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 m 6 A and other epitranscriptomic marks-including m 5 C, Ψ, N 7 -methylguanosine (m 7 G), N 1 -methyladenosine (m 1 A), N 4 -acetylcytidine (ac 4 C), and N 6 -2'-O-methyladenosine (m 6 Am) -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.

Source: Theranostics

DOI: 10.7150/thno.124482