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Publication : NCOR1 Orchestrates Transcriptional Landscapes and Effector Functions of CD4<sup>+</sup> T Cells.

First Author  Hainberger D Year  2020
Journal  Front Immunol Volume  11
Pages  579 PubMed ID  32318068
Mgi Jnum  J:305382 Mgi Id  MGI:6706245
Doi  10.3389/fimmu.2020.00579 Citation  Hainberger D, et al. (2020) NCOR1 Orchestrates Transcriptional Landscapes and Effector Functions of CD4(+) T Cells. Front Immunol 11:579
abstractText  The differentiation of naive 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 naive 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 IFNgamma 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 IFNgamma(+) and IFNgamma(+)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.
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