Empowering Regulatory T Cells in Autoimmunity

Regulatory T cells (Tregs) are capable of dampening immune-mediated inflammation and avert the destructive effects of uncontrolled inflammation. Distinct molecules and pathways, including various transcription factors, phosphatases, and kinases, impact the ability of Tregs to function as negative regulators of the immune response, and are presumably amenable to therapeutic manipulation. Here, we discuss recently identified molecular networks and the therapeutic potential for treating autoimmune diseases.

TrendsAfter differentiation in either the thymus or at peripheral sites, Tregs are capable of losing forkhead box P3 (FoxP3) expression and producing proinflammatory cytokines that potentially contribute to autoimmunity and inflammation.There are many epigenetic and transcriptional programs driven by the T cell receptor and interleukin 2 to protect the expression of Foxp3 in an inflammatory setting. Many new potential therapies to treat autoimmune or inflammatory conditions are aimed at maintaining epigenetic stability.The PI3K-Akt-mammalian target of rapamycin (mTOR) pathway is differentially modulated in Tregs compared with effector T cells and represents a promising therapeutic target to functionally empower Tregs to suppress inflammation.New and important insights have been obtained regarding the requirement for phosphatases and kinases in integrating cellular and metabolic signals within Tregs during autoimmune diseases.