NF-κB subunits RelA and c-Rel selectively control CD4+ T cell function in multiple sclerosis and cancer - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Experimental Medicine Année : 2024

NF-κB subunits RelA and c-Rel selectively control CD4+ T cell function in multiple sclerosis and cancer

Nathalie Davoust
Julie Caramel
Ulf Klein

Résumé

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.

Domaines

Immunologie
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Dates et versions

hal-04567979 , version 1 (03-05-2024)

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Guilhem Lalle, Raphaëlle Lautraite, Khaled Bouherrou, Maud Plaschka, Aurora Pignata, et al.. NF-κB subunits RelA and c-Rel selectively control CD4+ T cell function in multiple sclerosis and cancer. Journal of Experimental Medicine, 2024, 221 (6), ⟨10.1084/jem.20231348⟩. ⟨hal-04567979⟩
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