Plasticity of Treg cells: Is reprogramming of Treg cells possible in the presence of FOXP3?

Regulatory T cells (Treg cells) are involved in self tolerance, immune homeostasis, prevention of autoimmunity, and suppression of immunity to pathogens or tumors. The forkhead transcription factor FOXP3 is essential for Treg-cell development and function as mutations in FOXP3 cause severe autoimmune diseases in mice and humans. Over the last years it has been postulated that FOXP3 expression in Treg prevents effector T-cell (Teffector-cell) lineage commitment, yet several recent studies suggest that the co-existence of effector and regulatory T-cell programs can occur and might help to enable Treg cells with properties necessary to exert their function in peripheral tissues. Furthermore, downregulation of FOXP3 in the periphery might help Treg cells to lose suppressive functions and gain memory properties with specificity for self-antigens and an effector phenotype including the ability to produce IFN-γ and IL-17. This plasticity might have an impact on their reactivity towards autoimmunity as well as tumors or infections.