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

Frontiers in immunology 2020

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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. Copyright © 2020 Hainberger, Stolz, Zhu, Schuster, Müller, Hamminger, Rica, Waltenberger, Alteneder, Krausgruber, Hladik, Knapp, Bock, Trauner, Farrar and Ellmeier.

Citation

Daniela Hainberger, Valentina Stolz, Ci Zhu, Michael Schuster, Lena Müller, Patricia Hamminger, Ramona Rica, Darina Waltenberger, Marlis Alteneder, Thomas Krausgruber, Anastasiya Hladik, Sylvia Knapp, Christoph Bock, Michael Trauner, Michael A Farrar, Wilfried Ellmeier. NCOR1 Orchestrates Transcriptional Landscapes and Effector Functions of CD4+ T Cells. Frontiers in immunology. 2020;11:579