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

Sep 28, 2026

Uploaded by Oliver

RNA modifications form a versatile post-transcriptional regulatory layer that helps T lymphocytes precisely tune gene expression in development, environmental exposure, and pathogenic challenges. Chemical marks such as m6A, m5C, and pseudouridine shape transcript stability, splicing, localization, and translation via writer, reader, and eraser proteins. Evidence shows these pathways control lineage specification, activation thresholds, effector-memory balance, and immune tolerance, with dysregulation driving infection, autoimmunity, malignancy, and graft rejection. This review integrates m6A and additional epitranscriptomic marks—including m7G, m1A, ac4C, and m6Am—to connect shared molecular circuits governing transcriptional, metabolic, and signaling networks to disease progression. It also highlights open challenges like defining spatiotemporal modification landscapes and achieving selective pharmacological modulation, proposing integrative multi-omics and in vivo perturbation strategies for targeted immunotherapies.

LanguageEnglish

CategoryHealthcare

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Pages22

Reading Time55 min

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Abstract

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Introduction

Theranostics 2026, Vol. 16, Issue 5 2576 Ivyspring International Publisher Theranostics 2026; 16(5): 2576-2597. doi: 10.7150/thno.124482 Review RNA Modifications in T cell Immunity: Mechanisms, Disease Relevance, and Therapeutic Potential Xinyuan Zhao\#, Meiyan Zou\#, Weiyao Feng, Nina Li, Xu Chen, Pei Lin, Zihao Zhou, Yunfan Lin, Li Cui􀀍 Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China. \# Equal contributors. 􀀍 Corresponding author: Li Cui, Email: [licui@smu.edu.cn](licui@smu.edu.cn). © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions. Received: 2025.08.31; Accepted: 2025.11.27; Published: 2026.01.01 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 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 (m6Am)—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-omicsand in vivo perturbation approaches to translate epitranscriptomic mechanisms into targeted immunotherapies. | | | --- | --- | | Keywords: RNA modifications, T cell immunity, therapeutic potential, epitranscriptomics, immune regulation
Introduction | | | T lymphocytes constitute the cornerstone of adaptive immunity, orchestrating antigen-specific recognition, clonal expansion, and effector responses that collectively ensure the elimination of infected or malignant cells while maintaining immune tolerance and tissue homeostasis [1-3] . Their capacity to mount precise and flexible immune responses relies on the coordinated interplay of multiple regulatory layers, encompassing transcriptional, epigenetic, posttranscriptional, and metabolic control [4-6] . These mechanisms operate in an integrated and temporally synchronized manner to align T cell activation, differentiation, and resolution of effector responses with immunological demands. Disruption of this multilayered regulation can result in either immune insufficiency or immunopathology, underscoring the necessity for precise control mechanisms that enable T | cells to dynamically adapt to diverse environmental and pathogenic cues [7, 8] .
Among these regulatory dimensions, posttranscriptional control is particularly crucial. Following antigen encounter, T cells must rapidly remodel their transcriptome and proteome t

FAQs

How do RNA modifications regulate T cell gene expression?

RNA modifications add chemical marks to transcripts that influence stability, splicing, localization, and translation. This enables T cells to fine-tune gene expression in response to developmental, environmental, and pathogenic cues.

Which RNA marks are emphasized in the review?

The review highlights m6A, m5C, pseudouridine (Ψ) and also integrates m7G, m1A, ac4C, and m6Am. These marks act through writer, reader, and eraser proteins to coordinate RNA function.

What happens when RNA modification pathways become dysregulated?

Dysregulation can disrupt T cell fate and function, contributing to infection, autoimmunity, malignancy, and graft rejection. It can alter cytokine profiles, mitochondrial metabolism, and antigen-driven responses.

Sep 28, 2026

Uploaded by Oliver