Lalle, G. orcid.org/0000-0002-8861-9523, Lautraite, R. orcid.org/0000-0002-3437-5666, Bouherrou, K. orcid.org/0009-0005-4116-5180 et al. (24 more authors) (2024) NF-κB subunits RelA and c-Rel selectively control CD4+ T cell function in multiple sclerosis and cancer. Journal of Experimental Medicine, 221 (6). e20231348. ISSN 0022-1007
Abstract
The outcome of cancer and autoimmunity is often dictated by the effector functions of CD4+ conventional T cells (Tconv). Although activation of the NF-κB signaling pathway has long been implicated in Tconv biology, the cell-autonomous roles of the separate NF-κB transcription-factor subunits are unknown. Here, we dissected the contributions of the canonical NF-κB subunits RelA and c-Rel to Tconv function. RelA, rather than c-Rel, regulated Tconv activation and cytokine production at steady-state and was required for polarization toward the TH17 lineage in vitro. Accordingly, RelA-deficient mice were fully protected against neuroinflammation in a model of multiple sclerosis due to defective transition to a pathogenic TH17 gene-expression program. Conversely, Tconv-restricted ablation of c-Rel impaired their function in the microenvironment of transplanted tumors, resulting in enhanced cancer burden. Moreover, Tconv required c-Rel for the response to PD-1-blockade therapy. Our data reveal distinct roles for canonical NF-κB subunits in different disease contexts, paving the way for subunit-targeted immunotherapies.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2024 Lalle et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
Keywords: | CD4-Positive T-Lymphocytes; Animals; Mice; Neoplasms; Multiple Sclerosis; NF-kappa B; Proto-Oncogene Proteins c-rel; Signal Transduction; Tumor Microenvironment |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Medical Research (LIMR) > Division of Haematology and Immunology |
Depositing User: | Symplectic Publications |
Date Deposited: | 28 Jan 2025 10:59 |
Last Modified: | 28 Jan 2025 10:59 |
Status: | Published |
Publisher: | Rockefeller University Press |
Identification Number: | 10.1084/jem.20231348 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222450 |