Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-758
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dc.contributor.authorCastor, Timo-
dc.contributor.authorYogev, Nir-
dc.contributor.authorBlank, Thomas-
dc.contributor.authorBarwig, Christina-
dc.contributor.authorPrinz, Marco-
dc.contributor.authorWaisman, Ari-
dc.contributor.authorBros, Matthias-
dc.contributor.authorReske-Kunz, Angelika B.-
dc.date.accessioned2018-11-26T14:46:30Z-
dc.date.available2018-11-26T15:46:30Z-
dc.date.issued2018-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/760-
dc.description.abstractIn this study we analysed the effects of prophylactic biolistic DNA vaccination with plasmids encoding the encephalitogenic protein myelin oligodendrocyte glycoprotein (MOG) on the severity of a subsequently MOGp35-55-induced EAE and on the underlying immune response. We compared the outcome of vaccination with MOG-encoding plasmids alone or in combination with vectors encoding the regulatory cytokines IL-10 and TGF-ß1, respectively. MOG expression was restricted to skin dendritic cells (DCs) by the use of the DC-specific promoter of the fascin1 gene (pFscn-MOG). For comparison, the strong and ubiquitously active CMV promoter was employed (pCMV-MOG), which allows MOG expression in all transfected cells. Expression of IL-10 and TGF-ß1 was controlled by the CMV promoter to yield maximal synthesis (pCMV-IL10, pCMV-TGFß). Co-application of pFscn-MOG and pCMV IL10 significantly ameliorated EAE pathology, while vaccination with pCMV-MOG plus pCMV-IL10 did not affect EAE outcome. In contrast, vaccination with either of the two MOG-encoding plasmids in combination with pCMV-TGFß significantly attenuated the clinical EAE symptoms. Mechanistically, we observed diminished infiltration of Th17 and Th1 cells as well as macrophages/DCs into the CNS, which correlated with decreased MOGp35-55-specific production of IL-17 and IFN-ϫ by spleen cells and reduced peptide-specific T cell proliferation. Our findings suggest deletion of or anergy induction in MOG-specific CD4 T cells by the suppressive vaccination platform employed. MOG expression driven by the DC-specific fascin1 promoter yielded similar inhibitory effects on EAE progression as the ubiquitously active viral CMV promoter, when coapplying pCMV-TGFß. Our finding that pCMV-IL10 promoted tolerogenic effects only, when coapplied with pFscn-MOG, but not pCMV-MOG suggests that IL-10 affected only directly transfected DCs (pFscn-MOG), but not neighbouring DCs that engulfed MOG-containing vesicles derived from transfected keratinocytes (pCMV-MOG). Thus, due to its DC-restricted expression, the fascin1 promoter might be an interesting alternative to ubiquitously expressed promoters for vaccination strategies.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin-
dc.language.isoeng-
dc.rightsCC BYde_DE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleInhibition of experimental autoimmune encephalomyelitis by tolerance-promoting DNA vaccination focused to dendritic cellsen_GB
dc.typeZeitschriftenaufsatzde_DE
dc.identifier.urnurn:nbn:de:hebis:77-publ-586577-
dc.identifier.doihttp://doi.org/10.25358/openscience-758-
jgu.type.dinitypearticle-
jgu.type.versionPublished versionen_GB
jgu.type.resourceText-
jgu.organisation.departmentFB 04 Medizin-
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titlePLOS ONE-
jgu.journal.volume13-
jgu.journal.issue2-
jgu.pages.alternativee0191927-
jgu.publisher.year2018-
jgu.publisher.namePLOS-
jgu.publisher.placeSan Francisco, California, US-
jgu.publisher.urihttp://dx.doi.org/10.1371/journal.pone.0191927-
jgu.publisher.issn1932-6203-
jgu.organisation.placeMainz-
jgu.subject.ddccode610-
opus.date.accessioned2018-11-26T14:46:30Z-
opus.date.modified2018-11-28T09:14:38Z-
opus.date.available2018-11-26T15:46:30-
opus.subject.dfgcode00-000-
opus.organisation.stringFB 04: Medizin: Institut für Molekulare Medizinde_DE
opus.organisation.stringFB 04: Medizin: Hautklinikde_DE
opus.identifier.opusid58657-
opus.institute.number0458-
opus.institute.number0431-
opus.metadataonlyfalse-
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_GB
opus.affiliatedWaisman, Ari-
opus.affiliatedBros, Matthias-
opus.affiliatedReske-Kunz, Angelika B.-
jgu.publisher.doi10.1371/journal.pone.0191927
Appears in collections:JGU-Publikationen

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