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000137048 0247_ $$2doi$$a10.1084/jem.20122143
000137048 0247_ $$2pmid$$apmid:23999498
000137048 0247_ $$2pmc$$apmc:PMC3782053
000137048 0247_ $$2ISSN$$a0022-1007
000137048 0247_ $$2ISSN$$a1540-9358
000137048 0247_ $$2ISSN$$a1540-9538
000137048 037__ $$aDZNE-2020-03370
000137048 041__ $$aEnglish
000137048 082__ $$a610
000137048 1001_ $$0P:(DE-HGF)0$$aKreutzfeldt, Mario$$b0
000137048 245__ $$aNeuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss.
000137048 260__ $$aNew York, NY$$bRockefeller Univ. Press$$c2013
000137048 264_1 $$2Crossref$$3online$$bRockefeller University Press$$c2013-09-02
000137048 264_1 $$2Crossref$$3print$$bRockefeller University Press$$c2013-09-23
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000137048 520__ $$aNeurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators and structural consequences of CD8(+) T lymphocyte (CTL) attack on neurons in vivo. In a viral encephalitis model in mice, disease depended on CTL-derived interferon-γ (IFN-γ) and neuronal IFN-γ signaling. Downstream STAT1 phosphorylation and nuclear translocation in neurons were associated with dendrite and synapse loss (deafferentation). Analogous molecular and structural alterations were also found in human Rasmussen encephalitis, a CTL-mediated human autoimmune disorder of the CNS. Importantly, therapeutic intervention by IFN-γ blocking antibody prevented neuronal deafferentation and clinical disease without reducing CTL responses or CNS infiltration. These findings identify neuronal IFN-γ signaling as a novel target for neuroprotective interventions in CTL-mediated CNS disease.
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000137048 650_7 $$2NLM Chemicals$$aReceptors, Interferon
000137048 650_7 $$2NLM Chemicals$$aSTAT1 Transcription Factor
000137048 650_7 $$2NLM Chemicals$$afas Receptor
000137048 650_7 $$007MXG07O12$$2NLM Chemicals$$ainterferon gamma receptor
000137048 650_7 $$0126465-35-8$$2NLM Chemicals$$aPerforin
000137048 650_7 $$082115-62-6$$2NLM Chemicals$$aInterferon-gamma
000137048 650_2 $$2MeSH$$aAdolescent
000137048 650_2 $$2MeSH$$aAdult
000137048 650_2 $$2MeSH$$aAnimals
000137048 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: immunology
000137048 650_2 $$2MeSH$$aCell Nucleus: metabolism
000137048 650_2 $$2MeSH$$aChild
000137048 650_2 $$2MeSH$$aDendrites: immunology
000137048 650_2 $$2MeSH$$aHumans
000137048 650_2 $$2MeSH$$aInterferon-gamma: antagonists & inhibitors
000137048 650_2 $$2MeSH$$aInterferon-gamma: metabolism
000137048 650_2 $$2MeSH$$aLymphocytic Choriomeningitis: immunology
000137048 650_2 $$2MeSH$$aLymphocytic Choriomeningitis: metabolism
000137048 650_2 $$2MeSH$$aLymphocytic Choriomeningitis: prevention & control
000137048 650_2 $$2MeSH$$aLymphocytic choriomeningitis virus: immunology
000137048 650_2 $$2MeSH$$aMice
000137048 650_2 $$2MeSH$$aMice, Transgenic
000137048 650_2 $$2MeSH$$aNeurons: immunology
000137048 650_2 $$2MeSH$$aNeurons: metabolism
000137048 650_2 $$2MeSH$$aNeurons: virology
000137048 650_2 $$2MeSH$$aPerforin: genetics
000137048 650_2 $$2MeSH$$aPerforin: metabolism
000137048 650_2 $$2MeSH$$aPhosphorylation
000137048 650_2 $$2MeSH$$aProtein Transport
000137048 650_2 $$2MeSH$$aReceptors, Interferon: genetics
000137048 650_2 $$2MeSH$$aReceptors, Interferon: metabolism
000137048 650_2 $$2MeSH$$aSTAT1 Transcription Factor: metabolism
000137048 650_2 $$2MeSH$$aSignal Transduction
000137048 650_2 $$2MeSH$$aSpinal Cord: immunology
000137048 650_2 $$2MeSH$$aSpinal Cord: metabolism
000137048 650_2 $$2MeSH$$aSpinal Cord: pathology
000137048 650_2 $$2MeSH$$aSynapses: immunology
000137048 650_2 $$2MeSH$$aT-Lymphocytes, Cytotoxic: immunology
000137048 650_2 $$2MeSH$$aYoung Adult
000137048 650_2 $$2MeSH$$afas Receptor: genetics
000137048 650_2 $$2MeSH$$afas Receptor: metabolism
000137048 7001_ $$0P:(DE-HGF)0$$aBergthaler, Andreas$$b1
000137048 7001_ $$0P:(DE-HGF)0$$aFernandez, Marylise$$b2
000137048 7001_ $$0P:(DE-HGF)0$$aBrück, Wolfgang$$b3
000137048 7001_ $$0P:(DE-HGF)0$$aSteinbach, Karin$$b4
000137048 7001_ $$0P:(DE-HGF)0$$aVorm, Mariann$$b5
000137048 7001_ $$0P:(DE-HGF)0$$aCoras, Roland$$b6
000137048 7001_ $$0P:(DE-HGF)0$$aBlümcke, Ingmar$$b7
000137048 7001_ $$0P:(DE-HGF)0$$aBonilla, Weldy V$$b8
000137048 7001_ $$0P:(DE-HGF)0$$aFleige, Anne$$b9
000137048 7001_ $$0P:(DE-HGF)0$$aForman, Ruth$$b10
000137048 7001_ $$0P:(DE-HGF)0$$aMüller, Werner$$b11
000137048 7001_ $$0P:(DE-HGF)0$$aBecher, Burkhard$$b12
000137048 7001_ $$0P:(DE-2719)2810727$$aMisgeld, Thomas$$b13$$udzne
000137048 7001_ $$0P:(DE-HGF)0$$aKerschensteiner, Martin$$b14
000137048 7001_ $$0P:(DE-HGF)0$$aPinschewer, Daniel D$$b15
000137048 7001_ $$0P:(DE-HGF)0$$aMerkler, Doron$$b16$$eCorresponding author
000137048 77318 $$2Crossref$$3journal-article$$a10.1084/jem.20122143$$b : Rockefeller University Press, 2013-09-02$$n10$$p2087-2103$$tThe Journal of Experimental Medicine$$v210$$x1540-9538$$y2013
000137048 773__ $$0PERI:(DE-600)1477240-1$$a10.1084/jem.20122143$$gVol. 210, no. 10, p. 2087 - 2103$$n10$$p2087-2103$$q210:10<2087 - 2103$$tJournal of experimental medicine$$v210$$x1540-9538$$y2013
000137048 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782053
000137048 909CO $$ooai:pub.dzne.de:137048$$pVDB
000137048 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810727$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b13$$kDZNE
000137048 9131_ $$0G:(DE-HGF)POF3-341$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$aDE-HGF$$bForschungsbereich Gesundheit$$lErkrankungen des Nervensystems$$vMolecular Signaling$$x0
000137048 9141_ $$y2013
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