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dc.contributor.authorWang, Xu
dc.contributor.authorMulas, Floriana
dc.contributor.authorYi, Wenjing
dc.contributor.authorBrunn, Anna
dc.contributor.authorNishanth, Gopala
dc.contributor.authorJust, Sissy
dc.contributor.authorWaisman, Ari
dc.contributor.authorBrück, Wolfgang
dc.contributor.authorDeckert, Martina
dc.contributor.authorSchlüter, Dirk
dc.date.accessioned2020-08-17T13:55:37Z
dc.date.available2020-08-17T13:55:37Z
dc.date.issued2019-04-03
dc.identifier.citationEMBO J. 2019;38(10):e100947. doi:10.15252/embj.2018100947.en_US
dc.identifier.pmid30944096
dc.identifier.doi10.15252/embj.2018100947
dc.identifier.urihttp://hdl.handle.net/10033/622411
dc.description.abstractAstrocytes are critical regulators of neuroinflammation in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Growing evidence indicates that ubiquitination of signaling molecules is an important cell-intrinsic mechanism governing astrocyte function during MS and EAE Here, we identified an upregulation of the deubiquitinase OTU domain, ubiquitin aldehyde binding 1 (OTUB1) in astrocytes during MS and EAE Mice with astrocyte-specific OTUB1 ablation developed more severe EAE due to increased leukocyte accumulation, proinflammatory gene transcription, and demyelination in the spinal cord as compared to control mice. OTUB1-deficient astrocytes were hyperactivated in response to IFN-γ, a fingerprint cytokine of encephalitogenic T cells, and produced more proinflammatory cytokines and chemokines than control astrocytes. Mechanistically, OTUB1 inhibited IFN-γ-induced Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling by K48 deubiquitination and stabilization of the JAK2 inhibitor suppressor of cytokine signaling 1 (SOCS1). Thus, astrocyte-specific OTUB1 is a critical inhibitor of neuroinflammation in CNS autoimmunity.en_US
dc.language.isoenen_US
dc.publisherEMBO Pressen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectOTUB1en_US
dc.subjectastrocyteen_US
dc.subjectexperimental autoimmune encephalomyelitisen_US
dc.subjectmultiple sclerosisen_US
dc.subjectneuroinflammationen_US
dc.subjectubiquitinationen_US
dc.titleOTUB1 inhibits CNS autoimmunity by preventing IFN-γ-induced hyperactivation of astrocytes.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.identifier.eissn1460-2075
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalThe EMBO journalen_US
dc.source.volume38
dc.source.issue10
refterms.dateFOA2020-08-17T13:55:37Z
dc.source.journaltitleThe EMBO journal
dc.source.countryEngland


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