{"doi":"10.1084/jem.20231348","title":"NF-κB subunits RelA and c-Rel selectively control CD4+ T cell function in multiple sclerosis and cancer","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.","journal":"The Journal of Experimental Medicine","year":2024,"id":426394,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1225297,"name":"Raphaëlle Lautraite","orcid":"0000-0002-3437-5666","position":1,"is_corresponding":false},{"id":1225808,"name":"Khaled Bouherrou","orcid":null,"position":2,"is_corresponding":false},{"id":1225298,"name":"Maud Plaschka","orcid":"0000-0003-1137-7623","position":3,"is_corresponding":false},{"id":1225299,"name":"Aurora Pignata","orcid":"0000-0002-9806-1498","position":4,"is_corresponding":false},{"id":1019372,"name":"Allison Voisin","orcid":"0000-0003-0715-9391","position":5,"is_corresponding":false},{"id":1225300,"name":"Julie Twardowski","orcid":"0009-0006-4788-1193","position":6,"is_corresponding":false},{"id":1225301,"name":"Marlène Perrin-Niquet","orcid":"0009-0006-1496-4590","position":7,"is_corresponding":false},{"id":1225302,"name":"Pierre Stéphan","orcid":"0000-0001-5999-284X","position":8,"is_corresponding":false},{"id":1225303,"name":"Sarah Durget","orcid":"0009-0002-6484-4037","position":9,"is_corresponding":false},{"id":1225304,"name":"Laurie Tonon","orcid":"0009-0005-8794-7276","position":10,"is_corresponding":false},{"id":1209027,"name":"Maude Ardin","orcid":null,"position":11,"is_corresponding":false},{"id":1225305,"name":"Cyril Dégletagne","orcid":"0000-0002-5363-2381","position":12,"is_corresponding":false},{"id":14177,"name":"Alain Viari","orcid":"0000-0002-1329-7777","position":13,"is_corresponding":false},{"id":1225809,"name":"Laurence Belgarbi Dutron","orcid":null,"position":14,"is_corresponding":false},{"id":1225810,"name":"Nathalie Davoust","orcid":null,"position":15,"is_corresponding":false},{"id":566220,"name":"Thomas S. 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