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Heightened TLR7 signaling primes BCR-activated B cells in chronic graft-versus-host disease for effector functions

dc.rights.licenseopenen_US
dc.contributor.authorBRACKEN, Sonali J.
dc.contributor.authorSUTHERS, Amy N.
dc.contributor.authorDICIOCCIO, Rachel A.
dc.contributor.authorSU, Hsuan
dc.contributor.authorANAND, Sarah
dc.contributor.authorPOE, Jonathan C.
dc.contributor.authorJIA, Wei
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorVISENTIN, Jonathan
dc.contributor.authorBASHER, Fahmin
dc.contributor.authorJORDAN, Collin Z.
dc.contributor.authorMCMANIGLE, William C.
dc.contributor.authorLI, Zhiguo
dc.contributor.authorHAKIM, Frances T.
dc.contributor.authorPAVLETIC, Steven Z.
dc.contributor.authorBHUIYA, Nazmim S.
dc.contributor.authorHO, Vincent T.
dc.contributor.authorHORWITZ, Mitchell E.
dc.contributor.authorCHAO, Nelson J.
dc.contributor.authorSARANTOPOULOS, Stefanie
dc.date.accessioned2025-02-03T08:31:19Z
dc.date.available2025-02-03T08:31:19Z
dc.date.issued2024-01
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/204696
dc.description.abstractEnChronic graft-versus-host disease (cGVHD) is a debilitating, autoimmune-like syndrome that can occur after allogeneic hematopoietic stem cell transplantation. Constitutively activated B cells contribute to ongoing alloreactivity and autoreactivity in patients with cGVHD. Excessive tissue damage that occurs after transplantation exposes B cells to nucleic acids in the extracellular environment. Recognition of endogenous nucleic acids within B cells can promote pathogenic B-cell activation. Therefore, we hypothesized that cGVHD B cells aberrantly signal through RNA and DNA sensors such as Toll-like receptor 7 (TLR7) and TLR9. We found that B cells from patients and mice with cGVHD had higher expression of TLR7 than non-cGVHD B cells. Using ex vivo assays, we found that B cells from patients with cGVHD also demonstrated increased interleukin-6 production after TLR7 stimulation with R848. Low-dose B-cell receptor (BCR) stimulation augmented B-cell responses to TLR7 activation. TLR7 hyperresponsiveness in cGVHD B cells correlated with increased expression and activation of the downstream transcription factor interferon regulatory factor 5. Because RNA-containing immune complexes can activate B cells through TLR7, we used a protein microarray to identify RNA-containing antigen targets of potential pathological relevance in cGVHD. We found that many of the unique targets of active cGVHD immunoglobulin G (IgG) were nucleic acid–binding proteins. This unbiased assay identified the autoantigen and known cGVHD target Ro-52, and we found that RNA was required for IgG binding to Ro-52. Herein, we find that BCR-activated B cells have aberrant TLR7 signaling responses that promote potential effector responses in cGVHD.
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.title.enHeightened TLR7 signaling primes BCR-activated B cells in chronic graft-versus-host disease for effector functions
dc.typeArticle de revueen_US
dc.identifier.doi10.1182/bloodadvances.2023010362en_US
dc.subject.halSciences du Vivant [q-bio]/Immunologieen_US
dc.identifier.pubmed38113462en_US
bordeaux.journalBLOOD ADVANCESen_US
bordeaux.page667 – 680en_US
bordeaux.volume8en_US
bordeaux.hal.laboratoriesImmunoConcEpT - UMR 5164en_US
bordeaux.issue3en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-04925991
hal.version1
hal.date.transferred2025-02-03T08:31:23Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccCC BY-NC-NDen_US
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