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Impaired Autoimmune T Helper 17 Cell Responses Following DNA Vaccination against Rat Experimental Autoimmune Encephalomyelitis

BACKGROUND: We have previously shown that vaccination with DNA encoding the encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)(91–108) (pMOG) suppresses MOG(91–108)-induced rat Experimental Autoimmune Encephalomyelitis (EAE), a model for human Multiple Sclerosis (MS). The suppressive...

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Autores principales: Andersson, Åsa, Isaksson, Magnus, Wefer, Judit, Norling, Anna, Flores-Morales, Amilcar, Rorsman, Fredrik, Kämpe, Olle, Harris, Robert A., Lobell, Anna
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577303/
https://www.ncbi.nlm.nih.gov/pubmed/18997868
http://dx.doi.org/10.1371/journal.pone.0003682
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author Andersson, Åsa
Isaksson, Magnus
Wefer, Judit
Norling, Anna
Flores-Morales, Amilcar
Rorsman, Fredrik
Kämpe, Olle
Harris, Robert A.
Lobell, Anna
author_facet Andersson, Åsa
Isaksson, Magnus
Wefer, Judit
Norling, Anna
Flores-Morales, Amilcar
Rorsman, Fredrik
Kämpe, Olle
Harris, Robert A.
Lobell, Anna
author_sort Andersson, Åsa
collection PubMed
description BACKGROUND: We have previously shown that vaccination with DNA encoding the encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)(91–108) (pMOG) suppresses MOG(91–108)-induced rat Experimental Autoimmune Encephalomyelitis (EAE), a model for human Multiple Sclerosis (MS). The suppressive effect of pMOG is dependent on inclusion of CpG DNA in the plasmid backbone and is associated with early induction of Interferon (IFN)-β. PRINCIPAL FINDINGS: In this study we examined the mechanisms underlying pMOG-induced protection. We found that in the DNA vaccinated cohort proinflammatory Interleukin (IL)-17 and IL-21 responses were dramatically reduced compared to in the control group, but that the expression of Foxp3 and Tumor Growth Factor (TGF)-β1, which are associated with regulatory T cells, was not enhanced. Moreover, genes associated with Type I IFNs were upregulated. To delineate the role of IFN-β in the protective mechanism we employed short interfering RNA (siRNA) to IFN-β in the DNA vaccine. SiRNA to IFN-β completely abrogated the protective effects of the vaccine, demonstrating that a local early elaboration of IFN-β is important for EAE protection. IL-17 responses comparable to those in control rats developed in rats injected with the IFN-β-silencing DNA vaccine. CONCLUSIONS: We herein demonstrate that DNA vaccination protects from proinflammatory Th17 cell responses during induction of EAE. The mechanism involves IFN-β as IL-17 responses are rescued by silencing of IFN-β during DNA vaccination.
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spelling pubmed-25773032008-11-10 Impaired Autoimmune T Helper 17 Cell Responses Following DNA Vaccination against Rat Experimental Autoimmune Encephalomyelitis Andersson, Åsa Isaksson, Magnus Wefer, Judit Norling, Anna Flores-Morales, Amilcar Rorsman, Fredrik Kämpe, Olle Harris, Robert A. Lobell, Anna PLoS One Research Article BACKGROUND: We have previously shown that vaccination with DNA encoding the encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)(91–108) (pMOG) suppresses MOG(91–108)-induced rat Experimental Autoimmune Encephalomyelitis (EAE), a model for human Multiple Sclerosis (MS). The suppressive effect of pMOG is dependent on inclusion of CpG DNA in the plasmid backbone and is associated with early induction of Interferon (IFN)-β. PRINCIPAL FINDINGS: In this study we examined the mechanisms underlying pMOG-induced protection. We found that in the DNA vaccinated cohort proinflammatory Interleukin (IL)-17 and IL-21 responses were dramatically reduced compared to in the control group, but that the expression of Foxp3 and Tumor Growth Factor (TGF)-β1, which are associated with regulatory T cells, was not enhanced. Moreover, genes associated with Type I IFNs were upregulated. To delineate the role of IFN-β in the protective mechanism we employed short interfering RNA (siRNA) to IFN-β in the DNA vaccine. SiRNA to IFN-β completely abrogated the protective effects of the vaccine, demonstrating that a local early elaboration of IFN-β is important for EAE protection. IL-17 responses comparable to those in control rats developed in rats injected with the IFN-β-silencing DNA vaccine. CONCLUSIONS: We herein demonstrate that DNA vaccination protects from proinflammatory Th17 cell responses during induction of EAE. The mechanism involves IFN-β as IL-17 responses are rescued by silencing of IFN-β during DNA vaccination. Public Library of Science 2008-11-10 /pmc/articles/PMC2577303/ /pubmed/18997868 http://dx.doi.org/10.1371/journal.pone.0003682 Text en Andersson et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Andersson, Åsa
Isaksson, Magnus
Wefer, Judit
Norling, Anna
Flores-Morales, Amilcar
Rorsman, Fredrik
Kämpe, Olle
Harris, Robert A.
Lobell, Anna
Impaired Autoimmune T Helper 17 Cell Responses Following DNA Vaccination against Rat Experimental Autoimmune Encephalomyelitis
title Impaired Autoimmune T Helper 17 Cell Responses Following DNA Vaccination against Rat Experimental Autoimmune Encephalomyelitis
title_full Impaired Autoimmune T Helper 17 Cell Responses Following DNA Vaccination against Rat Experimental Autoimmune Encephalomyelitis
title_fullStr Impaired Autoimmune T Helper 17 Cell Responses Following DNA Vaccination against Rat Experimental Autoimmune Encephalomyelitis
title_full_unstemmed Impaired Autoimmune T Helper 17 Cell Responses Following DNA Vaccination against Rat Experimental Autoimmune Encephalomyelitis
title_short Impaired Autoimmune T Helper 17 Cell Responses Following DNA Vaccination against Rat Experimental Autoimmune Encephalomyelitis
title_sort impaired autoimmune t helper 17 cell responses following dna vaccination against rat experimental autoimmune encephalomyelitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577303/
https://www.ncbi.nlm.nih.gov/pubmed/18997868
http://dx.doi.org/10.1371/journal.pone.0003682
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