Improving regulatory T cell-based therapy: insights into post-translational modification regulation

Regulatory T (Treg) cells are pivotal for maintaining immune homeostasis and play essential roles in various diseases, such as autoimmune diseases, graft-versus-host disease (GVHD), tumors, and infectious diseases. Treg cells exert suppressive function via distinct mechanisms, including inhibitory cytokines, granzyme or perforin-mediated cytolysis, metabolic disruption, and suppression of dendritic cells. Forkhead Box P3 (FOXP3), the characteristic transcription factor, is essential for Treg cell function and plasticity. Cumulative evidence has demonstrated that FOXP3 activity and Treg cell function are modulated by a variety of post-translational modifications (PTMs), including ubiquitination, acetylation, phosphorylation, methylation, glycosylation, poly(ADP-ribosyl)ation, and uncharacterized modifications. This review describes Treg cell suppressive mechanisms and summarizes the current evidence on PTM regulation of FOXP3 and Treg cell function. Understanding the regulatory role of PTMs in Treg cell plasticity and function will be helpful in designing therapeutic strategies for autoimmune diseases, GVHD, tumors, and infectious diseases.