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OX40L/OX40 axis impairs follicular and natural Treg function in human SLE

dc.rights.licenseopenen_US
dc.contributor.authorJACQUEMIN, Clement
dc.contributor.authorAUGUSTO, Jean-Francois
dc.contributor.authorSCHERLINGER, Marc
dc.contributor.authorGENSOUS, Noemie
dc.contributor.authorFORCADE, Edouard
dc.contributor.authorDOUCHET, Isabelle
dc.contributor.authorLEVIONNOIS, Emeline
dc.contributor.authorRICHEZ, Christophe
dc.contributor.authorLAZARO, Estibaliz
dc.contributor.authorDUFFAU, Pierre
dc.contributor.authorTRUCHETET, Marie Elise
dc.contributor.authorSENESCHAL, Julien
dc.contributor.authorCOUZI, Lionel
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorPELLEGRIN, Jean-Luc
dc.contributor.authorVIALLARD, Jean-Francois
dc.contributor.authorSCHAEVERBEKE, Thierry
dc.contributor.authorPASCUAL, Virginia
dc.contributor.authorCONTIN BORDES, Cecile
dc.contributor.authorBLANCO, Patrick
dc.date.accessioned2020-11-17T15:46:41Z
dc.date.available2020-11-17T15:46:41Z
dc.date.issued2018-12-20
dc.identifier.issn2379-3708en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/14072
dc.description.abstractEnTregs are impaired in human systemic lupus erythematosus (SLE) and contribute to effector T cell activation. However, the mechanisms responsible for the Treg deficiency in SLE remain unclear. We hypothesized that the OX40L/OX40 axis is implicated in Treg and regulatory follicular helper T (Tfr) cell dysfunction in human SLE. OX40L/OX40 axis engagement on Tregs and Tfr cells not only specifically impaired their ability to regulate effector T cell proliferation, but also their ability to suppress T follicular helper (Tfh) cell-dependent B cell activation and immunoglobulin secretion. Antigen-presenting cells from patients with active SLE mediated Treg dysfunction in an OX40L-dependent manner, and OX40L-expressing cells colocalized with Foxp3+ cells in active SLE skin lesions. Engagement of the OX40L/OX40 axis resulted in Foxp3 downregulation in Tregs, and expression in SLE Tregs correlated with the proportion of circulating OX40L-expressing myeloid DCs. These data support that OX40L/OX40 signals are implicated in Treg dysfunction in human SLE. Thus, blocking the OX40L/OX40 axis appears to be a promising therapeutic strategy.
dc.language.isoENen_US
dc.subject.enMORPH3Eus
dc.title.enOX40L/OX40 axis impairs follicular and natural Treg function in human SLE
dc.title.alternativeJCI Insighten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1172/jci.insight.122167en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed30568041en_US
bordeaux.journalJCI insighten_US
bordeaux.volume3en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue24en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamMORPH3Eusen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
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