TET Proteins in the Spotlight: Emerging Concepts of Epigenetic Regulation in T Cell Biology

Ten-eleven translocation (TET) proteins are dioxygenases that oxidize 5-methylcytosine to form 5-hydroxymethylcytosine and downstream oxidized modified cytosines. In the past decade, intensive research established that TET-mediated DNA demethylation is critical for immune cell development and function. In this study, we discuss major advances regarding the role of TET proteins in regulating gene expression in the context of T cell lineage specification, function, and proliferation. Then, we focus on open questions in the field. We discuss recent findings regarding the diverse roles of TET proteins in other systems, and we ask how these findings might relate to T cell biology. Finally, we ask how this tremendous progress on understanding the multifaceted roles of TET proteins in shaping T cell identity and function can be translated to improve outcomes of human disease, such as hematological malignancies and immune response to cancer.