Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-758Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Castor, Timo | - |
| dc.contributor.author | Yogev, Nir | - |
| dc.contributor.author | Blank, Thomas | - |
| dc.contributor.author | Barwig, Christina | - |
| dc.contributor.author | Prinz, Marco | - |
| dc.contributor.author | Waisman, Ari | - |
| dc.contributor.author | Bros, Matthias | - |
| dc.contributor.author | Reske-Kunz, Angelika B. | - |
| dc.date.accessioned | 2018-11-26T14:46:30Z | - |
| dc.date.available | 2018-11-26T15:46:30Z | - |
| dc.date.issued | 2018 | - |
| dc.identifier.uri | https://openscience.ub.uni-mainz.de/handle/20.500.12030/760 | - |
| dc.description.abstract | In 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.sponsorship | DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin | - |
| dc.language.iso | eng | - |
| dc.rights | CC BY | de_DE |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
| dc.subject.ddc | 610 Medizin | de_DE |
| dc.subject.ddc | 610 Medical sciences | en_GB |
| dc.title | Inhibition of experimental autoimmune encephalomyelitis by tolerance-promoting DNA vaccination focused to dendritic cells | en_GB |
| dc.type | Zeitschriftenaufsatz | de_DE |
| dc.identifier.urn | urn:nbn:de:hebis:77-publ-586577 | - |
| dc.identifier.doi | http://doi.org/10.25358/openscience-758 | - |
| jgu.type.dinitype | article | - |
| jgu.type.version | Published version | en_GB |
| jgu.type.resource | Text | - |
| jgu.organisation.department | FB 04 Medizin | - |
| jgu.organisation.number | 2700 | - |
| jgu.organisation.name | Johannes Gutenberg-Universität Mainz | - |
| jgu.rights.accessrights | openAccess | - |
| jgu.journal.title | PLOS ONE | - |
| jgu.journal.volume | 13 | - |
| jgu.journal.issue | 2 | - |
| jgu.pages.alternative | e0191927 | - |
| jgu.publisher.year | 2018 | - |
| jgu.publisher.name | PLOS | - |
| jgu.publisher.place | San Francisco, California, US | - |
| jgu.publisher.uri | http://dx.doi.org/10.1371/journal.pone.0191927 | - |
| jgu.publisher.issn | 1932-6203 | - |
| jgu.organisation.place | Mainz | - |
| jgu.subject.ddccode | 610 | - |
| opus.date.accessioned | 2018-11-26T14:46:30Z | - |
| opus.date.modified | 2018-11-28T09:14:38Z | - |
| opus.date.available | 2018-11-26T15:46:30 | - |
| opus.subject.dfgcode | 00-000 | - |
| opus.organisation.string | FB 04: Medizin: Institut für Molekulare Medizin | de_DE |
| opus.organisation.string | FB 04: Medizin: Hautklinik | de_DE |
| opus.identifier.opusid | 58657 | - |
| opus.institute.number | 0458 | - |
| opus.institute.number | 0431 | - |
| opus.metadataonly | false | - |
| opus.type.contenttype | Keine | de_DE |
| opus.type.contenttype | None | en_GB |
| opus.affiliated | Waisman, Ari | - |
| opus.affiliated | Bros, Matthias | - |
| opus.affiliated | Reske-Kunz, Angelika B. | - |
| jgu.publisher.doi | 10.1371/journal.pone.0191927 | |
| jgu.organisation.ror | https://ror.org/023b0x485 | |
| Appears in collections: | JGU-Publikationen | |
