Immunosuppressive regulatory T cells (Tregs) are critical in maintaining immune tolerance and homeostasis of the immune system. Treg dysfunction leads to autoimmunity, while active Tregs in the tumor microenvironment hinders anti-tumor immune responses. As a master transcription factor of Tregs, forkhead box P3 (Foxp3) coordinates with different proteins in regulating Treg development and function. Such events are controlled by a series of post-translational modifications (PTMs). Among them, ubiquitin-dependent modifications of Foxp3 regulate degradation, nuclear localization, signal transduction, and suppressive function of the protein. Research has discovered different partners involved in the ubiquitination and deubiquitination of Foxp3. Understanding the mechanisms of these key PTMs of Foxp3 shall expand our knowledge of Tregs and pave the way for targeting Tregs in treating autoimmune diseases and cancer.
Autoimmunity, Clinical immunology, Immune cells and organs, Immunotherapy, Tumor immunology