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

by Bock, Christoph , Hamminger, Patricia , Hainberger, Daniela , Krausgruber, Thomas , Zhu, Ci , Trauner, Michael , Knapp, Sylvia , Ellmeier, Wilfried , Rica, Ramona , Schuster, Michael , Hladik, Anastasiya , Waltenberger, Darina , Alteneder, Marlis , Stolz, Valentina , Müller, Lena , Farrar, Michael A.

in Adoptive Transfer / Animals / Antibodies / CD4 antigen / CD4+ T cells / CD4-Positive T-Lymphocytes - immunology / Cell differentiation / Cell Differentiation - immunology / Cell growth / Cell survival / Chromatin / Colitis / Colitis - immunology / corepressor / Cytokines / Epigenetics / Gene expression / Helper cells / Immunity (Disease) / Immunology / interferon γ / Laboratory animals / Lymphocytes / Lymphocytes T / Metabolism / Mice / NCOR1 / Nuclear Receptor Co-Repressor 1 - immunology / Peptides / T helper differentiation / Th1 Cells - immunology / Th17 Cells - immunology / Thyroid gland / Transcription factors / Transcription, Genetic / Transcriptomes / Transgenic animals / γ-Interferon

2020

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

2020

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

2020

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Journal Article

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

Bock, Christoph,

Hamminger, Patricia,

Hainberger, Daniela,

Krausgruber, Thomas,

Zhu, Ci,

Trauner, Michael,

Knapp, Sylvia,

Ellmeier, Wilfried,

Rica, Ramona,

Schuster, Michael,

Hladik, Anastasiya,

Waltenberger, Darina,

Alteneder, Marlis,

Stolz, Valentina,

Müller, Lena,

Farrar, Michael A.

2020

Overview

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

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Publisher

Frontiers Media SA,Frontiers Media S.A

Subject

/ Animals

/ CD4-Positive T-Lymphocytes - immunology

/ Cell differentiation