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. |