Transcriptional mechanisms that regulate T helper 1 cell differentiation

Recent research has made great strides in uncovering the mechanisms by which the T helper 1 (Th1) cell gene expression program is established. In particular, studies examining the transcription factors T-bet, STAT1, and STAT4 have elucidated their roles in regulating Th1 signature genes, including Ifng, and have started to address their contributions to the epigenetic states in Th1 cells. Additionally, new findings have provided information about how the co-expression of T helper cell lineage-defining transcription factors impacts the phenotype of the cell. In this review, we will briefly highlight the research from the last few years examining the epigenetic states in T helper cells and the mechanisms by which they are established. We will then discuss how this new information contributes to our understanding of the flexibility of T helper cell genetic programs.

► T-bet, STAT1, and STAT4 are required for Th1 cell differentiation.
► Epigenetic studies have changed our concept of T helper cell stability/flexibility.
► T-bet interacts with the H3K27-demethylase Jmjd3.
► T-bet interacts with several permissive chromatin remodeling complexes.
► Co-expression of T-bet with other lineage-defining factors impacts Th1 development.