SCHERLINGER, Marc; GUILLOTIN, Vivien; DOUCHET, Isabelle; VACHER, Pierre; BOIZARD MORACCHINI, Andrea; GUEGAN, Jean-Philippe; GARREAU, Anne; MERILLON, Nathalie; VERMOREL, Agathe; RIBEIRO, Emmanuel; MACHELART, Irene; LAZARO, Estibaliz; COUZI, Lionel; DUFFAU, Pierre; BARNETCHE, Thomas; PELLEGRIN, Jean-Luc; VIALLARD, Jean-Francois; SALEH, Maya; SCHAEVERBEKE, Thierry; LEGEMBRE, Patrick; TRUCHETET, Marie-Elise; DUMORTIER, Helene; CONTIN-BORDES, Cecile; SISIRAK, Vanja; RICHEZ, Christophe; BLANCO, Patrick

doi:10.1126/scitranslmed.abi4994

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SCHERLINGER, Marc

Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

GUILLOTIN, Vivien
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

DOUCHET, Isabelle
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

SCHERLINGER, Marc

Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

GUILLOTIN, Vivien
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

DOUCHET, Isabelle
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

VACHER, Pierre

BOIZARD MORACCHINI, Andrea

Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

GUEGAN, Jean-Philippe

GARREAU, Anne

Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

MERILLON, Nathalie
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

Bordeaux population health [BPH]

VIALLARD, Jean-Francois

SALEH, Maya

Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

SCHAEVERBEKE, Thierry

LEGEMBRE, Patrick

TRUCHETET, Marie-Elise
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

DUMORTIER, Helene

CONTIN-BORDES, Cecile
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

SISIRAK, Vanja

Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

RICHEZ, Christophe

Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

BLANCO, Patrick

Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]

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Science Translational Medicine. 2021-06-30, vol. 13, n° 600

Résumé en anglais

Systemic 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.< Réduire

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https://oskar-bordeaux.fr/handle/20.500.12278/110199

DOI

http://dx.doi.org/10.1126/scitranslmed.abi4994

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

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

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