The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability.
NF-κB
activation
autoimmunity
regulatory T cells
relA
stability
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2019
2019
Historique:
received:
16
06
2019
accepted:
04
10
2019
entrez:
22
11
2019
pubmed:
22
11
2019
medline:
30
10
2020
Statut:
epublish
Résumé
Regulatory T cells (Tregs) play a major role in immune homeostasis and in the prevention of autoimmune diseases. It has been shown that c-Rel is critical in Treg thymic differentiation, but little is known on the role of NF-κB on mature Treg biology. We thus generated mice with a specific knockout of RelA, a key member of NF-κB, in Tregs. These mice developed a severe autoimmune syndrome with multi-organ immune infiltration and high activation of lymphoid and myeloid cells. Phenotypic and transcriptomic analyses showed that RelA is critical in the acquisition of the effector Treg state independently of surrounding inflammatory environment. Unexpectedly, RelA-deficient Tregs also displayed reduced stability and cells that had lost Foxp3 produced inflammatory cytokines. Overall, we show that RelA is critical for Treg biology as it promotes both the generation of their effector phenotype and the maintenance of their identity.
Identifiants
pubmed: 31749798
doi: 10.3389/fimmu.2019.02487
pmc: PMC6842949
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
Transcription Factor RelA
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2487Subventions
Organisme : NIAID NIH HHS
ID : R01 AI116834
Pays : United States
Informations de copyright
Copyright © 2019 Ronin, Lubrano di Ricco, Vallion, Divoux, Kwon, Grégoire, Collares, Rouers, Baud, Benoist and Salomon.
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