A T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitis
Abstract 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...
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2021-10-01
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doaj-e703d43485cd4415ac33af46ed0a0b4b2021-10-10T11:26:39ZengNature Publishing GroupScientific Reports2045-23222021-10-0111111110.1038/s41598-021-99134-xA T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitisGuilhem Lalle0Raphaëlle Lautraite1Allison Voisin2Julie Twardowski3Pierre Stéphan4Marlène Perrin-Niquet5Ramdane Igalouzene6Saidi M. Soudja7Julien C. Marie8Marc Vocanson9Nilushi De Silva10Ulf Klein11Sankar Ghosh12Yenkel Grinberg-Bleyer13Cancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardCancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardCancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardCancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardCancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardCancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardCancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardCancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardCancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardCIRI-Centre International de Recherche en Infectiologie, INSERM, U1111, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR 5308Immunity and Cancer Department, Institut Curie, Paris-Sciences-Et-Lettres Research UniversityDivision of Haematology and Immunology, Leeds Institute of Medical Research at St. James’s, University of LeedsDepartment of Microbiology and Immunology, College of Physicians and Surgeons, Columbia UniversityCancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Labex DEVweCAN, Centre Léon BérardAbstract 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.https://doi.org/10.1038/s41598-021-99134-x |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 |
author_facet |
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 |
author_sort |
Guilhem Lalle |
title |
A T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitis |
title_short |
A T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitis |
title_full |
A T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitis |
title_fullStr |
A T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitis |
title_full_unstemmed |
A T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitis |
title_sort |
t cell-intrinsic function for nf-κb relb in experimental autoimmune encephalomyelitis |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-10-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1038/s41598-021-99134-x |
work_keys_str_mv |
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