The effects of post-translational modifications on Th17/Treg cell differentiation.

Regulatory T (Treg) cells and Th17 cells are subsets of CD4 T cells which play an essential role in immune homeostasis and infection. Dysregulation of the Th17/Treg cell balance was shown to be implicated in the development and progression of several disorders such as autoimmune disease, inflammatory disease, and cancer. Multiple factors, including T cell receptor (TCR) signals, cytokines, metabolic and epigenetic regulators can influence the differentiation of Th17 and Treg cells and affect their balance. Accumulating evidence indicates that the activity of key molecules such as forkhead box P3 (Foxp3), the retinoic acid-related orphan receptor gamma t (RORγt), and signal transducer and activator of transcription (STAT)s are modulated by the number of post-translational modifications (PTMs) such as phosphorylation, methylation, nitrosylation, acetylation, glycosylation, lipidation, ubiquitination, and SUMOylation. PTMs might affect the protein folding efficiency and protein conformational stability, and consequently determine protein structure, localization, and function. Here, we review the recent progress in our understanding of how PTMs modify the key molecules involved in the Th17/Treg cell differentiation, regulate the Th17/Treg balance, and initiate autoimmune diseases caused by dysregulation of the Th17/Treg balance. A better understanding of Th17/Treg regulation may help to develop novel potential therapeutics to treat immune-related diseases.