Astrocytic DLL4-NOTCH1 signaling pathway promotes neuroinflammation via the IL-6-STAT3 axis.
| dc.rights.license | open | en_US |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | MORA, Pierre | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | LAISNÉ, Margaux | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | BOURGUIGNON, Célia | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | ROUAULT, Paul | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | JASPARD-VINASSA, Béatrice | |
| hal.structure.identifier | Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB] | |
| dc.contributor.author | MAÎTRE, Marlène | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | GADEAU, Alain-Pierre | |
| dc.contributor.author | RENAULT, Marie-Ange | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | HORNG, Sam | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | COUFFINHAL, Thierry | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | CHAPOULY, Candice | |
| dc.date.accessioned | 2024-10-16T07:15:44Z | |
| dc.date.available | 2024-10-16T07:15:44Z | |
| dc.date.issued | 2024-10-10 | |
| dc.identifier.issn | 1742-2094 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/202515 | |
| dc.description.abstractEn | Under neuroinflammatory conditions, astrocytes acquire a reactive phenotype that drives acute inflammatory injury as well as chronic neurodegeneration. We hypothesized that astrocytic Delta-like 4 (DLL4) may interact with its receptor NOTCH1 on neighboring astrocytes to regulate astrocyte reactivity via downstream juxtacrine signaling pathways. Here we investigated the role of astrocytic DLL4 on neurovascular unit homeostasis under neuroinflammatory conditions. We probed for downstream effectors of the DLL4-NOTCH1 axis and targeted these for therapy in two models of CNS inflammatory disease. We first demonstrated that astrocytic DLL4 is upregulated during neuroinflammation, both in mice and humans, driving astrocyte reactivity and subsequent blood-brain barrier permeability and inflammatory infiltration. We then showed that the DLL4-mediated NOTCH1 signaling in astrocytes directly drives IL-6 levels, induces STAT3 phosphorylation promoting upregulation of astrocyte reactivity markers, pro-permeability factor secretion and consequent blood-brain barrier destabilization. Finally we revealed that blocking DLL4 with antibodies improves experimental autoimmune encephalomyelitis symptoms in mice, identifying a potential novel therapeutic strategy for CNS autoimmune demyelinating disease. As a general conclusion, this study demonstrates that DLL4-NOTCH1 signaling is not only a key pathway in vascular development and angiogenesis, but also in the control of astrocyte reactivity during neuroinflammation. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.subject.en | Animals | |
| dc.subject.en | Astrocytes | |
| dc.subject.en | Receptor | |
| dc.subject.en | Notch1 | |
| dc.subject.en | STAT3 Transcription Factor | |
| dc.subject.en | Mice | |
| dc.subject.en | Signal Transduction | |
| dc.subject.en | Interleukin-6 | |
| dc.subject.en | Calcium-Binding Proteins | |
| dc.subject.en | Humans | |
| dc.subject.en | Mice | |
| dc.subject.en | Inbred C57BL | |
| dc.subject.en | Adaptor Proteins | |
| dc.subject.en | Signal Transducing | |
| dc.subject.en | Encephalomyelitis | |
| dc.subject.en | Autoimmune | |
| dc.subject.en | Experimental | |
| dc.subject.en | Blood-Brain Barrier | |
| dc.subject.en | Neuroinflammatory Diseases | |
| dc.subject.en | Cells | |
| dc.subject.en | Cultured | |
| dc.subject.en | Intracellular Signaling Peptides and Proteins | |
| dc.subject.en | Female | |
| dc.title.en | Astrocytic DLL4-NOTCH1 signaling pathway promotes neuroinflammation via the IL-6-STAT3 axis. | |
| dc.title.alternative | J Neuroinflammation | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1186/s12974-024-03246-w | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Cardiologie et système cardiovasculaire | en_US |
| dc.identifier.pubmed | 39390606 | en_US |
| bordeaux.journal | Journal of Neuroinflammation | en_US |
| bordeaux.page | 258 | en_US |
| bordeaux.volume | 21 | en_US |
| bordeaux.hal.laboratories | Biologie des maladies cardiovasculaires (BMC) - UMR 1034 | en_US |
| bordeaux.issue | 1 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | pubmed | |
| hal.identifier | hal-04739078 | |
| hal.version | 1 | |
| hal.date.transferred | 2024-10-16T07:15:50Z | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | true | |
| workflow.import.source | pubmed | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Neuroinflammation&rft.date=2024-10-10&rft.volume=21&rft.issue=1&rft.spage=258&rft.epage=258&rft.eissn=1742-2094&rft.issn=1742-2094&rft.au=MORA,%20Pierre&LAISN%C3%89,%20Margaux&BOURGUIGNON,%20C%C3%A9lia&ROUAULT,%20Paul&JASPARD-VINASSA,%20B%C3%A9atrice&rft.genre=article |
