Arginine methylation in immunoregulation: Mechanisms and therapeutic targeting.

Abstract

Post-translational modifications (PTMs) are central regulators of immune cell function, linking extracellular signals to the regulation of intracellular gene expression. Among these, protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is a key mechanism that connects epigenetic control with signal transduction. PRMTs modify both histone and non-histone substrates, thereby regulating chromatin accessibility, transcriptional programs, and immune signaling pathways. Recent studies have shown that arginine methylation modulates immune cell activation, differentiation, and effector functions, whereas its dysregulation contributes to tumor immune evasion and chronic inflammation. Notably, alterations in PRMT activity have been increasingly suggested in age-associated immune remodeling and inflammaging. In this review, we integrate current evidence showing how PRMT-mediated arginine methylation coordinates chromatin regulation, RNA metabolism, and immune signaling, and examine how these mechanisms shape immune homeostasis, tumor immunity, inflammaging, and opportunities for therapeutic intervention.