Bitte benutzen Sie diese Kennung, um auf die Ressource zu verweisen:
http://doi.org/10.25358/openscience-758
Autoren: | Castor, Timo Yogev, Nir Blank, Thomas Barwig, Christina Prinz, Marco Waisman, Ari Bros, Matthias Reske-Kunz, Angelika B. |
Titel: | Inhibition of experimental autoimmune encephalomyelitis by tolerance-promoting DNA vaccination focused to dendritic cells |
Online-Publikationsdatum: | 26-Nov-2018 |
Erscheinungsdatum: | 2018 |
Sprache des Dokuments: | Englisch |
Zusammenfassung/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. |
DDC-Sachgruppe: | 610 Medizin 610 Medical sciences |
Veröffentlichende Institution: | Johannes Gutenberg-Universität Mainz |
Organisationseinheit: | FB 04 Medizin |
Veröffentlichungsort: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-758 |
URN: | urn:nbn:de:hebis:77-publ-586577 |
Version: | Published version |
Publikationstyp: | Zeitschriftenaufsatz |
Nutzungsrechte: | CC BY |
Informationen zu den Nutzungsrechten: | https://creativecommons.org/licenses/by/4.0/ |
Zeitschrift: | PLOS ONE 13 2 |
Seitenzahl oder Artikelnummer: | e0191927 |
Verlag: | PLOS |
Verlagsort: | San Francisco, California, US |
Erscheinungsdatum: | 2018 |
ISSN: | 1932-6203 |
URL der Originalveröffentlichung: | http://dx.doi.org/10.1371/journal.pone.0191927 |
DOI der Originalveröffentlichung: | 10.1371/journal.pone.0191927 |
Enthalten in den Sammlungen: | JGU-Publikationen |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | ||
---|---|---|---|---|---|
58657.pdf | 6.16 MB | Adobe PDF | Öffnen/Anzeigen |