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dc.contributor.authorPeruzzotti Jametti, Lucaen
dc.contributor.authorBernstock, Joshuaen
dc.contributor.authorVicario, Nunzioen
dc.contributor.authorCosta, Ana SHen
dc.contributor.authorKwok, Chee Keongen
dc.contributor.authorLeonardi, Tommasoen
dc.contributor.authorBooty, Lee Men
dc.contributor.authorBicci, Iacopoen
dc.contributor.authorBalzarotti, Beatriceen
dc.contributor.authorVolpe, Giulioen
dc.contributor.authorMallucci, Giuliaen
dc.contributor.authorManferrari, Giuliaen
dc.contributor.authorDonegà, Matteoen
dc.contributor.authorIraci, Nunzioen
dc.contributor.authorBraga, Aliceen
dc.contributor.authorHallenbeck, John Men
dc.contributor.authorMurphy, Mikeen
dc.contributor.authorEdenhofer, Franken
dc.contributor.authorFrezza, Christianen
dc.contributor.authorPluchino, Stefanoen
dc.date.accessioned2018-04-23T10:07:10Z
dc.date.available2018-04-23T10:07:10Z
dc.date.issued2018-03en
dc.identifier.issn1934-5909
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/275108
dc.description.abstractNeural stem cell (NSC) transplantation can influence immune responses and suppress inflammation in the central nervous system (CNS). Metabolites such as succinate modulate the phenotype and function of immune cells, but whether and how NSCs are also activated by such immunometabolites to control immunoreactivity and inflammatory responses is unclear. Here we show that transplanted somatic and directly induced NSCs ameliorate chronic CNS inflammation by reducing succinate levels in the cerebrospinal fluid, thereby decreasing mononuclear phagocyte (MP) infiltration and secondary CNS damage. Inflammatory MPs release succinate which activates succinate receptor 1(SUCNR1)/GPR91 on NSCs, leading them to secrete prostaglandin E2 and scavenge extracellular succinate with consequential anti-inflammatory effects. Thus, our work reveals an unexpected role for the succinate-SUCNR1 axis in somatic and directly induced NSCs, which controls the response of stem cells to inflammatory metabolic signals released by type-1 MPs in the chronically inflamed brain.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCentral Nervous Systemen
dc.subjectCell Lineen
dc.subjectMacrophagesen
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectHumansen
dc.subjectChronic Diseaseen
dc.subjectInflammationen
dc.subjectSuccinic Aciden
dc.subjectDinoprostoneen
dc.subjectReceptors, G-Protein-Coupleden
dc.subjectOxidative Phosphorylationen
dc.subjectFemaleen
dc.subjectNeural Stem Cellsen
dc.titleMacrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation.en
dc.typeArticle
prism.endingPage368.e13
prism.issueIdentifier3en
prism.publicationDate2018en
prism.publicationNameCell stem cellen
prism.startingPage355
prism.volume22en
dc.identifier.doi10.17863/CAM.18797
dcterms.dateAccepted2018-01-25en
rioxxterms.versionofrecord10.1016/j.stem.2018.01.020en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-03en
dc.contributor.orcidPeruzzotti-Jametti, Luca [0000-0002-9396-5607]
dc.contributor.orcidBernstock, Joshua [0000-0002-7814-3867]
dc.contributor.orcidVicario, Nunzio [0000-0001-5934-3962]
dc.contributor.orcidCosta, Ana SH [0000-0001-8932-6370]
dc.contributor.orcidKwok, Chee Keong [0000-0003-3803-1200]
dc.contributor.orcidLeonardi, Tommaso [0000-0002-4449-1863]
dc.contributor.orcidBooty, Lee M [0000-0003-3003-5872]
dc.contributor.orcidBicci, Iacopo [0000-0001-6994-3857]
dc.contributor.orcidBalzarotti, Beatrice [0000-0002-5174-6625]
dc.contributor.orcidVolpe, Giulio [0000-0002-3891-2297]
dc.contributor.orcidMallucci, Giulia [0000-0002-0031-9594]
dc.contributor.orcidManferrari, Giulia [0000-0001-7062-1142]
dc.contributor.orcidIraci, Nunzio [0000-0003-2146-9329]
dc.contributor.orcidBraga, Alice [0000-0003-3273-9742]
dc.contributor.orcidMurphy, Michael [0000-0003-1115-9618]
dc.contributor.orcidEdenhofer, Frank [0000-0002-6489-714X]
dc.contributor.orcidFrezza, Christian [0000-0002-3293-7397]
dc.contributor.orcidPluchino, Stefano [0000-0002-6267-9472]
dc.identifier.eissn1875-9777
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_00015/3)
pubs.funder-project-idWellcome Trust (110159/Z/15/Z)
pubs.funder-project-idMRC (MC_U105663142)
pubs.funder-project-idMRC (MC_UU_12022/1_do not transfer?)
pubs.funder-project-idMedical Research Council (MC_UU_12022/6)
cam.orpheus.successThu Jan 30 12:59:06 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International