Original Research ARTICLE
The NF-κB RelA transcription factor is critical for regulatory T cell activation and stability
- 1INSERM U1135 Centre d'Immunologie et de Maladies Infectieuses, France
- 2Division of Immunology, Department of Immunology and Microbiology, Harvard Medical School, United States
- 3Université Paris Descartes, France
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.
Keywords: Regulatory T (Treg) cell, Stabililby, NFkB, Autoimmunity, activation
Received: 16 Jun 2019;
Accepted: 04 Oct 2019.
Copyright: © 2019 Ronin, Lubrano di Ricco, Vallion, Divoux, Kwom, Grégoire, Collares, Rouers, Baud, Benoist and Salomon. 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.
* Correspondence: Dr. Benoit L. Salomon, INSERM U1135 Centre d'Immunologie et de Maladies Infectieuses, Paris, 75013, Île-de-France, France, email@example.com