Cargando…
The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability
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 o...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842949/ https://www.ncbi.nlm.nih.gov/pubmed/31749798 http://dx.doi.org/10.3389/fimmu.2019.02487 |
_version_ | 1783468110898003968 |
---|---|
author | Ronin, Emilie Lubrano di Ricco, Martina Vallion, Romain Divoux, Jordane Kwon, Ho-Keun Grégoire, Sylvie Collares, Davi Rouers, Angéline Baud, Véronique Benoist, Christophe Salomon, Benoit L. |
author_facet | Ronin, Emilie Lubrano di Ricco, Martina Vallion, Romain Divoux, Jordane Kwon, Ho-Keun Grégoire, Sylvie Collares, Davi Rouers, Angéline Baud, Véronique Benoist, Christophe Salomon, Benoit L. |
author_sort | Ronin, Emilie |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6842949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68429492019-11-20 The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability Ronin, Emilie Lubrano di Ricco, Martina Vallion, Romain Divoux, Jordane Kwon, Ho-Keun Grégoire, Sylvie Collares, Davi Rouers, Angéline Baud, Véronique Benoist, Christophe Salomon, Benoit L. Front Immunol Immunology 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. Frontiers Media S.A. 2019-10-30 /pmc/articles/PMC6842949/ /pubmed/31749798 http://dx.doi.org/10.3389/fimmu.2019.02487 Text en Copyright © 2019 Ronin, Lubrano di Ricco, Vallion, Divoux, Kwon, Grégoire, Collares, Rouers, Baud, Benoist and Salomon. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Ronin, Emilie Lubrano di Ricco, Martina Vallion, Romain Divoux, Jordane Kwon, Ho-Keun Grégoire, Sylvie Collares, Davi Rouers, Angéline Baud, Véronique Benoist, Christophe Salomon, Benoit L. The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability |
title | The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability |
title_full | The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability |
title_fullStr | The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability |
title_full_unstemmed | The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability |
title_short | The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability |
title_sort | nf-κb rela transcription factor is critical for regulatory t cell activation and stability |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842949/ https://www.ncbi.nlm.nih.gov/pubmed/31749798 http://dx.doi.org/10.3389/fimmu.2019.02487 |
work_keys_str_mv | AT roninemilie thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT lubranodiriccomartina thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT vallionromain thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT divouxjordane thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT kwonhokeun thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT gregoiresylvie thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT collaresdavi thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT rouersangeline thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT baudveronique thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT benoistchristophe thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT salomonbenoitl thenfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT roninemilie nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT lubranodiriccomartina nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT vallionromain nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT divouxjordane nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT kwonhokeun nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT gregoiresylvie nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT collaresdavi nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT rouersangeline nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT baudveronique nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT benoistchristophe nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability AT salomonbenoitl nfkbrelatranscriptionfactoriscriticalforregulatorytcellactivationandstability |