The New Insight Into the Role of Transcription Factors in the Function of Regulatory T Cells With Emphasis on FOXP3 and Its Implication in the Treatment of Autoimmune Disorders

Peripheral immune tolerance is a cardinal feature of the adaptive immune system, which makes self-nonself discrimination and unresponsiveness toward self-antigens. Disruption in the regulation of these processes leads to damage to self-tissues and serious consequences, including autoimmune diseases. In the T cell compartment, the family of regulatory T cells (Treg cells) is the main component for the induction and maintenance of immune tolerance and preventing autoimmune diseases. Forkhead box P3 (FOXP3) is the key transcription factor for the function and Treg cell programming. Importantly, FOXP3 by itself is insufficient to completely specify the Treg cell program, suggesting that additional accessory transcription factors are involved both upstream and downstream, as well as alongside FOXP3, in directing Treg cell specification and its expression is controlled through various regulatory factors and epigenetic modifications. In the current review, we examine new insight into the regulatory mechanisms of Treg cell functions and programming with an emphasis on FOXP3, which opens new avenues for future therapeutic strategies of autoimmune disorders.