Tregs in Autoimmunity: Insights Into Intrinsic Brake Mechanism Driving Pathogenesis and Immune Homeostasis

CD4(+)CD25(high)Foxp3(+) regulatory T-cells (Tregs) are functionally characterized for their ability to suppress the activation of multiple immune cell types and are indispensable for maintaining immune homeostasis and tolerance. Disruption of this intrinsic brake system assessed by loss of suppressive capacity, cell numbers, and Foxp3 expression, leads to uncontrolled immune responses and tissue damage. The conversion of Tregs to a pathogenic pro-inflammatory phenotype is widely observed in immune mediated diseases. However, the molecular mechanisms that underpin the control of Treg stability and suppressive capacity are incompletely understood. This review summarizes the concepts of T-reg cell stability and T-reg cell plasticity highlighting underlying mechanisms including translational and epigenetic regulators that may enable translation to new therapeutic strategies. Our enhanced understanding of molecular mechanism controlling Tregs will have important implications into immune homeostasis and therapeutic potential for the treatment of immune-mediated diseases.

Automated summary

CD4 (+) CD25 (high) Foxp3 (+) regulatory T-cells (Tregs) play a crucial role in maintaining immune homeostasis and tolerance. This review summarizes the concept of Treg cell stability and plasticity, as well as the underlying molecular mechanisms, including translational and epigenetic regulators, which may contribute to the development of new therapeutic strategies.