Afficher la notice abrégée

Platelets release mitochondrial antigens in systemic lupus erythematosus

dc.rights.licenseopenen_US
dc.contributor.authorMELKI, Imene
dc.contributor.authorALLAEYS, Isabelle
dc.contributor.authorTESSANDIER, Nicolas
dc.contributor.authorLEVESQUE, Tania
dc.contributor.authorCLOUTIER, Nathalie
dc.contributor.authorLAROCHE, Audree
dc.contributor.authorVERNOUX, Nathalie
dc.contributor.authorBECKER, Yann
dc.contributor.authorBENK-FORTIN, Hadrien
dc.contributor.authorZUFFEREY, Anne
dc.contributor.authorROLLET-LABELLE, Emmanuelle
dc.contributor.authorPOULIOT, Marc
dc.contributor.authorPOIRIER, Guy
dc.contributor.authorPATEY, Natacha
dc.contributor.authorBELLEANNEE, Clemence
dc.contributor.authorSOULET, Denis
dc.contributor.authorMCKENZIE, Steven E.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorBRISSON, Alain
dc.contributor.authorTREMBLAY, Marie-Eve
dc.contributor.authorLOOD, Christian
dc.contributor.authorFORTIN, Paul R.
dc.contributor.authorBOILARD, Eric
dc.date.accessioned2021-07-09T15:41:40Z
dc.date.available2021-07-09T15:41:40Z
dc.date.issued2021
dc.identifier.issn1946-6234en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/106510
dc.description.abstractEnThe accumulation of DNA and nuclear components in blood and their recognition by autoantibodies play a central role in the pathophysiology of systemic lupus erythematosus (SLE). Despite the efforts, the sources of circulating autoantigens in SLE are still unclear. Here, we show that in SLE, platelets release mitochondrial DNA, the majority of which is associated with the extracellular mitochondrial organelle. Mitochondrial release in patients with SLE correlates with platelet degranulation. This process requires the stimulation of platelet Fc gamma RIIA, a receptor for immune complexes. Because mice lack Fc gamma RIIA and murine platelets are completely devoid of receptor capable of binding IgG-containing immune complexes, we used transgenic mice expressing Fc gamma RIIA for our in vivo investigations. Fc gamma RIIA expression in lupus-prone mice led to the recruitment of platelets in kidneys and to the release of mitochondria in vivo. Using a reporter mouse with red fluorescent protein targeted to the mitochondrion, we confirmed platelets as a source of extracellular mitochondria driven by Fc gamma RIIA and its cosignaling by the fibrinogen receptor alpha 2b beta 3 in vivo. These findings suggest that platelets might be a key source of mitochondrial antigens in SLE and might be a therapeutic target for treating SLE.
dc.language.isoENen_US
dc.title.enPlatelets release mitochondrial antigens in systemic lupus erythematosus
dc.typeArticle de revueen_US
dc.identifier.doi10.1126/scitranslmed.aav5928en_US
dc.subject.halChimie/Matériauxen_US
bordeaux.journalScience Translational Medicineen_US
bordeaux.volume13en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248en_US
bordeaux.issue581en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03283210
hal.version1
hal.date.transferred2021-07-09T15:41:45Z
hal.exporttrue
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Science%20Translational%20Medicine&rft.date=2021&rft.volume=13&rft.issue=581&rft.eissn=1946-6234&rft.issn=1946-6234&rft.au=MELKI,%20Imene&ALLAEYS,%20Isabelle&TESSANDIER,%20Nicolas&LEVESQUE,%20Tania&CLOUTIER,%20Nathalie&rft.genre=article


Fichier(s) constituant ce document

FichiersTailleFormatVue

Il n'y a pas de fichiers associés à ce document.

Ce document figure dans la(les) collection(s) suivante(s)

Afficher la notice abrégée