NFAT primes the human RORC locus for RORγt expression in CD4+ T cells

被引：0

作者：

Hanane Yahia-Cherbal

Magda Rybczynska

Domenica Lovecchio

Tharshana Stephen

Chloé Lescale

Katarzyna Placek

Jérome Larghero

Lars Rogge

Elisabetta Bianchi

机构：

[1] Institut Pasteur,Laboratoire Colloides et Matériaux Divisés

[2] Immunoregulation Unit,Immunology and Metabolism, LIMES Institute

[3] Department of Immunology,undefined

[4] Université Paris Diderot,undefined

[5] Sorbonne Paris Cité,undefined

[6] Cellule Pasteur,undefined

[7] Institut Pasteur,undefined

[8] Unité de Technologie et Service Cytométrie et Biomarqueurs (UTechS CB),undefined

[9] Centre de recherche translationnelle (CRT),undefined

[10] Institut Pasteur,undefined

[11] Genome Integrity,undefined

[12] Immunity and Cancer Unit,undefined

[13] Equipe Labellisée Ligue Contre le Cancer,undefined

[14] Department of Immunology,undefined

[15] Department of Genomes and Genetics,undefined

[16] Assistance Publique-Hopitaux de Paris,undefined

[17] Hôpital Saint-Louis,undefined

[18] Cell Therapy Unit and Cord Blood Bank; CIC de Biothérapies,undefined

[19] École supérieure de Physique et de Chimie industrielles,undefined

[20] University of Bonn,undefined

来源：

Nature Communications | / 10卷

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摘要：

T helper 17 (Th17) cells have crucial functions in mucosal immunity and the pathogenesis of several chronic inflammatory diseases. The lineage-specific transcription factor, RORγt, encoded by the RORC gene modulates Th17 polarization and function, as well as thymocyte development. Here we define several regulatory elements at the human RORC locus in thymocytes and peripheral CD4+ T lymphocytes, with CRISPR/Cas9-guided deletion of these genomic segments supporting their role in RORγt expression. Mechanistically, T cell receptor stimulation induces cyclosporine A-sensitive histone modifications and P300/CBP acetylase recruitment at these elements in activated CD4+ T cells. Meanwhile, NFAT proteins bind to these regulatory elements and activate RORγt transcription in cooperation with NF-kB. Our data thus demonstrate that NFAT specifically regulate RORγt expression by binding to the RORC locus and promoting its permissive conformation.

引用

共 113 条

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