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

Area of Science:

• Immunology
• Molecular Biology
• Epigenetics

Background:

• RNA modifications are crucial for post-transcriptional gene regulation in T lymphocytes.
• Chemical marks like N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), and pseudouridine (Ψ) influence transcript fate and T cell functions.
• Dysregulation of RNA modification pathways is linked to various diseases, including infections, autoimmunity, and cancer.

Purpose of the Study:

• To review the role of diverse RNA modifications in T cell immunity.
• To delineate how different epitranscriptomic marks converge on shared molecular circuits.
• To highlight the potential of RNA modifications as therapeutic targets in immune-related diseases.

Main Methods:

• Literature review integrating findings on various RNA modifications (m⁶A, m⁵C, Ψ, m⁷G, m¹A, ac⁴C, m⁶A_m).
• Analysis of how these modifications impact T cell lineage specification, activation, and function.
• Examination of the link between aberrant modification patterns and disease pathogenesis.

Main Results:

• RNA modifications orchestrate T cell development, activation thresholds, and immune balance.
• Distinct RNA modifications converge on molecular circuits controlling T cell transcriptional, metabolic, and signaling networks.
• Aberrant modification patterns alter cytokine profiles, metabolism, and immune responses, influencing disease outcomes.

Conclusions:

• RNA modification is a central regulatory axis linking transcriptomic plasticity to T cell immunity and therapeutic responsiveness.
• Targeting epitranscriptomic mechanisms holds promise for developing novel immunotherapies.
• Further research is needed to define spatiotemporal modification landscapes and develop selective pharmacological modulators.