NCOR1 Orchestrates Transcriptional Landscapes and Effector Functions of CD4 + T Cells

The differentiation of naïve CD4 T cells into T helper (Th) subsets is key for a functional immune response and has to be tightly controlled by transcriptional and epigenetic processes. However, the function of cofactors that connect gene-specific transcription factors with repressive chromatin-modifying enzymes in Th cells is yet unknown. Here we demonstrate an essential role for nuclear receptor corepressor 1 (NCOR1) in regulating naïve CD4 T cell and Th1/Th17 effector transcriptomes. Moreover, NCOR1 binds to a conserved -regulatory element within the locus and controls the extent of IFNγ expression in Th1 cells. Further, NCOR1 controls the survival of activated CD4 T cells and Th1 cells , while Th17 cell survival was not affected in the absence of NCOR1. , effector functions were compromised since adoptive transfer of NCOR1-deficient CD4 T cells resulted in attenuated colitis due to lower frequencies of IFNγ and IFNγ IL-17A Th cells and overall reduced CD4 T cell numbers. Collectively, our data demonstrate that the coregulator NCOR1 shapes transcriptional landscapes in CD4 T cells and controls Th1/Th17 effector functions.