A T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitis.

Scientific reports 2021 Oct 04

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NF-kappaB (NF-κB) is a family of transcription factors with pleiotropic functions in immune responses. The alternative NF-κB pathway that leads to the activation of RelB and NF-κB2, was previously associated with the activation and function of T cells, though the exact contribution of these NF-κB subunits remains unclear. Here, using mice carrying conditional ablation of RelB in T cells, we evaluated its role in the development of conventional CD4+ T (Tconv) cells and their function in autoimmune diseases. RelB was largely dispensable for Tconv cell homeostasis, activation and proliferation, and for their polarization toward different flavors of Thelper cells in vitro. Moreover, ablation of RelB had no impact on the capacity of Tconv cells to induce autoimmune colitis. Conversely, clinical severity of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS) was significantly reduced in mice with RelB-deficient T cells. This was associated with impaired expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically in the central nervous system. Our data reveal a discrete role for RelB in the pathogenic function of Tconv cells during EAE, and highlight this transcription factor as a putative therapeutic target in MS. © 2021. The Author(s).

Citation

Guilhem Lalle, Raphaëlle Lautraite, Allison Voisin, Julie Twardowski, Pierre Stéphan, Marlène Perrin-Niquet, Ramdane Igalouzene, Saidi M Soudja, Julien C Marie, Marc Vocanson, Nilushi De Silva, Ulf Klein, Sankar Ghosh, Yenkel Grinberg-Bleyer. A T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitis. Scientific reports. 2021 Oct 04;11(1):19674