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dc.rights.licenseopenen_US
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorNGUYEN KY, Melanie
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorDURAN, Adrien
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorHASANTARI, Iris
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorBRU, Agnès
hal.structure.identifierIBIO - Plateforme de bio-imagerie en sciences médicales
dc.contributor.authorDELOIRE, Mathilde
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorBROCHET, Bruno
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorRUET, Aurelie
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorSCHMITT, Nathalie
dc.date.accessioned2024-03-23T11:20:34Z
dc.date.available2024-03-23T11:20:34Z
dc.date.issued2023-09-22
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/188937
dc.description.abstractEnBACKGROUND AND OBJECTIVES: Natalizumab, a monoclonal humanized antibody targeting integrin α4, inhibits the transmigration of lymphocytes into the CNS by preventing the interaction of integrin α4β1 with V-CAM expressed on brain vascular endothelial cells. Although natalizumab treatment reduces the clinical relapse rate in patients with relapsing-remitting MS, its discontinuation after reactivation of the JC virus is associated with a rebound of the disease in 20% of patients. The mechanisms of this rebound are not elucidated, but natalizumab increases the frequencies of circulating CD4 T cells expressing proinflammatory cytokines as well as the proportion of circulating Th17/Th1 cells (Th1-like Th17 cells). Gut-derived memory CD4 T cells are a population of growing interest in the pathogenesis of MS, but whether and how their properties are affected by natalizumab is not known. Here, we studied the phenotype and cytokine expression profile of circulating gut-derived memory CD4 T cells in patients with relapsing-remitting MS under natalizumab. METHODS: We identified gut-derived memory CD4 T cells by their expression of integrin β7 and compared their properties and those of integrin β7- memory CD4 T cells across healthy donors and patients with relapsing-remitting MS treated or not with natalizumab. We also compared the capacity of integrin β7- and integrin β7+ CD4 T-cell subsets to transmigrate in vitro across a model of blood-brain barrier. RESULTS: The proportions of proinflammatory Th17/Th1 cells as well as of IL-17A+IFNγ+ and IL-17A+GM-CSF+ cells were higher in memory CD4 T cells expressing integrin β7 in patients receiving natalizumab compared with healthy donors and patients with relapsing-remitting MS not receiving natalizumab. By contrast, integrin β7 negative memory CD4 T cells only presented a modest increased in their proportion of Th17/Th1 cells under natalizumab. We further observed that integrin β7+ Th17/Th1 cells migrated as efficiently as integrin β7- Th17/Th1 across a monolayer of brain microvascular endothelial cells. DISCUSSION: Our study shows that circulating integrin β7+ memory CD4 T cells of patients with relapsing-remitting MS under natalizumab are enriched in proinflammatory cells supporting the hypothesis that integrin β7+ memory CD4 T cells could play a pathogenic role in the disease rebound observed at natalizumab discontinuation. Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
dc.description.sponsorshipInitiative d'excellence de l'Université de Bordeaux - ANR-10-IDEX-0003en_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enAntibodies
dc.subject.enMonoclonal
dc.subject.enCD4-Positive
dc.subject.enT-Lymphocytes
dc.subject.enEndothelial Cells
dc.subject.enHumans
dc.subject.enInterleukin-17
dc.subject.enNatalizumab / pharmacology
dc.title.enNatalizumab Treatment Induces Proinflammatory CD4 T Cells Preferentially in the Integrin β7+ Compartment
dc.title.alternativeNeurol Neuroimmunol Neuroinflammen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1212/NXI.0000000000200166en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed37739811en_US
bordeaux.journalNeurology(R) neuroimmunology & neuroinflammationen_US
bordeaux.volume10en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - U1215en_US
bordeaux.issue6en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.institutionINSERMen_US
bordeaux.teamRelations glie-neuroneen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDFondation pour l'Aide à la Recherche sur la Sclérose en Plaquesen_US
bordeaux.identifier.funderIDMinistère de l'Enseignement supérieur, de la Recherche et de l'Innovationen_US
hal.identifierhal-04518256
hal.version1
hal.date.transferred2024-03-23T11:20:37Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccCC BY-NC-NDen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Neurology(R)%20neuroimmunology%20&%20neuroinflammation&rft.date=2023-09-22&rft.volume=10&rft.issue=6&rft.au=NGUYEN%20KY,%20Melanie&DURAN,%20Adrien&HASANTARI,%20Iris&BRU,%20Agn%C3%A8s&DELOIRE,%20Mathilde&rft.genre=article


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