作者
Guilhem Lalle,Raphaëlle Lautraite,Khaled Bouherrou,Maud Plaschka,Aurora Pignata,Allison Voisin,Julie Twardowski,Marlène Perrin-Niquet,Pierre Stéphan,Sarah Durget,Laurie Tonon,Maude Ardin,Cyril Dégletagne,Alain Viari,Laurence Belgarbi Dutron,Nathalie Davoust,Thomas S. Postler,Jingyao Zhao,Christophe Caux,Julie Caramel,S. Dalle,Philippe Cassier,Ulf Klein,Marc Schmidt-Supprian,Roland Liblau,Sankar Ghosh,Yenkel Grinberg‐Bleyer
摘要
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.