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Selectins impair regulatory T cell function and contribute to systemic lupus erythematosus pathogenesis

dc.rights.licenseopenen_US
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorSCHERLINGER, Marc
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorGUILLOTIN, Vivien
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorDOUCHET, Isabelle
dc.contributor.authorVACHER, Pierre
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorBOIZARD MORACCHINI, Andrea
dc.contributor.authorGUEGAN, Jean-Philippe
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorGARREAU, Anne
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorMERILLON, Nathalie
dc.contributor.authorVERMOREL, Agathe
dc.contributor.authorRIBEIRO, Emmanuel
dc.contributor.authorMACHELART, Irene
dc.contributor.authorLAZARO, Estibaliz
dc.contributor.authorCOUZI, Lionel
dc.contributor.authorDUFFAU, Pierre
dc.contributor.authorBARNETCHE, Thomas
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorPELLEGRIN, Jean-Luc
dc.contributor.authorVIALLARD, Jean-Francois
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorSALEH, Maya
dc.contributor.authorSCHAEVERBEKE, Thierry
dc.contributor.authorLEGEMBRE, Patrick
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorTRUCHETET, Marie-Elise
dc.contributor.authorDUMORTIER, Helene
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorCONTIN-BORDES, Cecile
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorSISIRAK, Vanja
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorRICHEZ, Christophe
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorBLANCO, Patrick
dc.date.accessioned2021-08-24T08:51:08Z
dc.date.available2021-08-24T08:51:08Z
dc.date.issued2021-06-30
dc.identifier.issn1946-6234 (Print) 1946-6242 (Online)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/110199
dc.description.abstractEnSystemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, and a defect in the regulatory T (T(reg)) cell compartment. In this work, we identified that platelets from patients with active SLE preferentially interacted with T(reg) cells via the P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1) axis. Selectin interaction with PSGL-1 blocked the regulatory and suppressive properties of T(reg) cells and particularly follicular T(reg) cells by triggering Syk phosphorylation and an increase in intracytosolic calcium. Mechanistically, P-selectin engagement on T(reg) cells induced a down-regulation of the transforming growth factor-β axis, altering the phenotype of T(reg) cells and limiting their immunosuppressive responses. In patients with SLE, we found an up-regulation of P- and E-selectin both on microparticles and in their soluble forms that correlated with disease activity. Last, blocking P-selectin in a mouse model of SLE improved cardinal features of the disease, such as anti-dsDNA antibody concentrations and kidney pathology. Overall, our results identify a P-selectin-dependent pathway that is active in patients with SLE and validate it as a potential therapeutic avenue.
dc.language.isoENen_US
dc.title.enSelectins impair regulatory T cell function and contribute to systemic lupus erythematosus pathogenesis
dc.typeArticle de revueen_US
dc.identifier.doi10.1126/scitranslmed.abi4994en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed34193612en_US
bordeaux.journalScience Translational Medicineen_US
bordeaux.volume13en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue600en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.institutionCNRS
bordeaux.teamMORPH3Eusen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03324933
hal.version1
hal.date.transferred2021-08-24T08:51:15Z
hal.exporttrue
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