AUTHOR=Hainberger Daniela , Stolz Valentina , Zhu Ci , Schuster Michael , Müller Lena , Hamminger Patricia , Rica Ramona , Waltenberger Darina , Alteneder Marlis , Krausgruber Thomas , Hladik Anastasiya , Knapp Sylvia , Bock Christoph , Trauner Michael , Farrar Michael A. , Ellmeier Wilfried TITLE=NCOR1 Orchestrates Transcriptional Landscapes and Effector Functions of CD4+ T Cells JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00579 DOI=10.3389/fimmu.2020.00579 ISSN=1664-3224 ABSTRACT=

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 cis-regulatory element within the Ifng locus and controls the extent of IFNγ expression in Th1 cells. Further, NCOR1 controls the survival of activated CD4+ T cells and Th1 cells in vitro, while Th17 cell survival was not affected in the absence of NCOR1. In vivo, 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.