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

Front Immunol. 2020 Apr 3;11:579. doi: 10.3389/fimmu.2020.00579. eCollection 2020.

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.

Keywords: CD4+ T cells; NCOR1; T helper differentiation; colitis; corepressor; gene regulation; interferon γ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Colitis / immunology
  • Mice
  • Nuclear Receptor Co-Repressor 1 / immunology*
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Transcription, Genetic

Substances

  • Ncor1 protein, mouse
  • Nuclear Receptor Co-Repressor 1