Ubiquitination signals critical to regulatory T cell development and function.

Protein ubiquitination has emerged as a crucial modulator of the immune system, participating in the control of T cell differentiation, intracellular signal transduction and the induction of immune tolerance. CD4(+)CD25(+)FOXP3(+) regulatory T cells are a unique subset of cells that mediate central and peripheral immune tolerance. In this review, we highlight our current understanding of the molecular mechanisms and signaling pathways that modulate protein ubiquitination in Treg cells, and how ubiquitination determines Treg cell development and function. Understanding how FOXP3 activity is regulated by ubiquitination and deubiquitination under molecular level will promote regulatory T cell therapy for treating inflammation in autoimmune disease, infection, transplantation and cancer.