Epigenetic and transcriptional control of Foxp3+ regulatory T cells

Regulatory T cells (Treg cells) present a unique T-cell lineage that plays a key role for the initiation and maintenance of immunological tolerance. Treg cells are characterized by the expression of the forkhead box transcription factor Foxp3, which acts as a lineage-specifying factor and determines the unique properties of these immunosuppressive cells. Work over the past few years has shown that well-defined and precisely controlled events on transcriptional and epigenetic level are required to ensure stable expression of Foxp3 in Treg cells. More recent work suggested that in addition to stable Foxp3 expression, epigenetic modifications of Treg-cell specific genes contribute to the unique phenotype of Treg cells by imprinting their transcriptional program and stabilizing the expression of molecules being essential for the suppressive properties of Treg cells. In this review, we will highlight how Foxp3 expression itself is epigenetically and transcriptionally controlled, how the Treg-cell specific epigenetic signature is achieved, how Foxp3 as transcription factor influences the gene expression programs in Treg cells and how unique properties of Treg-cell subsets are defined by other transcription factors.