ThPOK, a Key Regulator of T Cell Development and Function

The molecular basis of differentiation of immature thymocyte precursors to alternate CD4 or CD8 lineage cells remains poorly understood, but appears to be controlled by differences in TCR signaling. Importantly, we have shown that the transcription factor ThPOK acts as a master regulator of this process, such that its presence or absence dictates development to the CD4 or CD8 lineages, respectively. We have also shown that ThPOK expression in thymocytes and mature T cells is regulated primarily at the transcriptional level via several stage- and lineage-specific cis elements. Of particular importance is the ultraconserved ThPOK silencer, whose deletion is sufficient to cause promiscuous expression of ThPOK in thymocytes and diversion of all developing thymocytes to the CD4 lineage. In this review, we provide an overview of the role of ThPOK in cd4 versus cd8 commitment, as well as its transcriptional 68regulation and additional important roles of ThPOK in development and function of other T cell subsets.