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Immunity. 2017 Sep 19;47(3):450-465.e5. doi: 10.1016/j.immuni.2017.08.010. Epub 2017 Sep 7.

An NF-κB Transcription-Factor-Dependent Lineage-Specific Transcriptional Program Promotes Regulatory T Cell Identity and Function.

Author information

1
Department of Microbiology & Immunology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
2
New York Genome Center, New York, NY 10013, USA.
3
Department of Systems Biology and Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
4
Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.
5
II Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität Munich, Munich, Germany.
6
Department of Microbiology & Immunology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA; Section of Dermatology, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, 03756, USA.
7
Department of Microbiology & Immunology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA; Department of Pathology & Cell Biology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.
8
Department of Microbiology & Immunology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA. Electronic address: sg2715@cumc.columbia.edu.

Abstract

Both conventional T (Tconv) cells and regulatory T (Treg) cells are activated through ligation of the T cell receptor (TCR) complex, leading to the induction of the transcription factor NF-κB. In Tconv cells, NF-κB regulates expression of genes essential for T cell activation, proliferation, and function. However the role of NF-κB in Treg function remains unclear. We conditionally deleted canonical NF-κB members p65 and c-Rel in developing and mature Treg cells and found they have unique but partially redundant roles. c-Rel was critical for thymic Treg development while p65 was essential for mature Treg identity and maintenance of immune tolerance. Transcriptome and NF-κB p65 binding analyses demonstrated a lineage specific, NF-κB-dependent transcriptional program, enabled by enhanced chromatin accessibility. These dual roles of canonical NF-κB in Tconv and Treg cells highlight the functional plasticity of the NF-κB signaling pathway and underscores the need for more selective strategies to therapeutically target NF-κB.

PMID:
28889947
PMCID:
PMC5679261
DOI:
10.1016/j.immuni.2017.08.010
[Indexed for MEDLINE]
Free PMC Article

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