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dc.contributor.authorKlammer, Markus G
dc.contributor.authorDzaye, Omar
dc.contributor.authorWallach, Thomas
dc.contributor.authorKrüger, Christina
dc.contributor.authorGaessler, Dorothea
dc.contributor.authorBuonfiglioli, Alice
dc.contributor.authorDerkow, Katja
dc.contributor.authorKettenmann, Helmut
dc.contributor.authorBrinkmann, Melanie M
dc.contributor.authorLehnardt, Seija
dc.date.accessioned2021-11-16T15:17:59Z
dc.date.available2021-11-16T15:17:59Z
dc.date.issued2021-09-13
dc.identifier.citationFront Immunol. 2021 Sep 13;12:715774. doi: 10.3389/fimmu.2021.715774.en_US
dc.identifier.pmid34589086
dc.identifier.doi10.3389/fimmu.2021.715774
dc.identifier.urihttp://hdl.handle.net/10033/623098
dc.description.abstractThe chaperone protein Unc-93 homolog B1 (UNC93B1) regulates internalization, trafficking, and stabilization of nucleic acid-sensing Toll-like receptors (TLR) in peripheral immune cells. We sought to determine UNC93B1 expression and its functional relevance in inflammatory and injurious processes in the central nervous system (CNS). We found that UNC93B1 is expressed in various CNS cells including microglia, astrocytes, oligodendrocytes, and neurons, as assessed by PCR, immunocyto-/histochemistry, and flow cytometry. UNC93B1 expression in the murine brain increased during development. Exposure to the microRNA let-7b, a recently discovered endogenous TLR7 activator, but also to TLR3 and TLR4 agonists, led to increased UNC93B1 expression in microglia and neurons. Microglial activation by extracellular let-7b required functional UNC93B1, as assessed by TNF ELISA. Neuronal injury induced by extracellular let-7b was dependent on UNC93B1, as UNC93B1-deficient neurons were unaffected by the microRNA's neurotoxicity in vitro. Intrathecal application of let-7b triggered neurodegeneration in wild-type mice, whereas mice deficient for UNC93B1 were protected against injurious effects on neurons and axons. In summary, our data demonstrate broad UNC93B1 expression in the murine brain and establish this chaperone as a modulator of neuroinflammation and neuronal injury triggered by extracellular microRNA and subsequent induction of TLR signaling.en_US
dc.language.isoenen_US
dc.publisherFrontiersen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectUNC93B1en_US
dc.subjectlet-7ben_US
dc.subjectmicroRNAen_US
dc.subjectmicrogliaen_US
dc.subjectneurodegenerationen_US
dc.subjectneuroinflammationen_US
dc.subjectneuronsen_US
dc.subjecttoll-like receptoren_US
dc.titleUNC93B1 Is Widely Expressed in the Murine CNS and Is Required for Neuroinflammation and Neuronal Injury Induced by MicroRNA .en_US
dc.typeArticleen_US
dc.identifier.eissn1664-3224
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalFrontiers in immunologyen_US
dc.source.volume12
dc.source.beginpage715774
dc.source.endpage
refterms.dateFOA2021-11-16T15:18:00Z
dc.source.journaltitleFrontiers in immunology
dc.source.countrySwitzerland


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