Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analog

Bibliographic Details
Main Author: Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]
Publication Date: 2017
Other Authors: Mimura, Luiza Ayumi Nishiyama [UNESP], Fraga-Silva, Thais Fernanda Campos [UNESP], Ishikawa, Larissa Lumi Watanabe [UNESP], França, Thais Graziela Donegá [UNESP], Sartori, Alexandrina [UNESP]
Format: Article
Language: eng
Source: Repositório Institucional da UNESP
Download full: http://dx.doi.org/10.3389/fimmu.2017.01198
http://hdl.handle.net/11449/175366
Summary: Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely employed to evaluate new strategies to control MS, including procedures to induce immunological tolerance. Considering that skin exposure to protein antigens can induce tolerance and that vitamin D analogs conserve immunomodulatory potential and are less toxic, we investigated the efficacy of epicutaneous application of a myelin oligodendrocyte glycoprotein peptide (MOG35-55) associated with paricalcitol (PARI) on EAE development. Three and 11 days after EAE induction, C57BL/6 mice were treated with an occlusive patch containing MOG plus PARI. Clinical parameters were daily assessed, whereas immunological and histological evaluations were performed during the acute EAE phase. MOG and MOG + PARI significantly controlled disease development reducing weight loss and clinical score. Moreover, MOG and MOG + PARI reduced the inflammatory process and preserved the myelin sheath in the CNS. High percentages of Foxp3+ regulatory T cells (Tregs) and lower MHCII fluorescence intensity in dendritic cells in draining lymph nodes were concomitantly observed. MOG + PARI association was, however, more efficient being able to reduce disease incidence and clinical scores more significantly than MOG or PARI alone. This experimental group also displayed a higher ratio between mRNA expression for Foxp3 and RORc and a higher percentage of Foxp3+ cells in the CNS. Modulation of activation markers observed in microglial cells eluted from EAE treated mice were confirmed by in vitro studies with the BV-2 microglial cell line. The results show that MOG + PARI association applied by an epicutaneous route controlled EAE development. Protective involved mechanisms include mainly a higher proportion of Tregs and also a direct immunomodulatory effect of PARI on microglial cells.
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spelling Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analogEpicutaneous routeExperimental autoimmune encephalomyelitisMOGRegulatory T cellVitamin D analogMultiple sclerosis (MS) is an inflammatory and demyelinating disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely employed to evaluate new strategies to control MS, including procedures to induce immunological tolerance. Considering that skin exposure to protein antigens can induce tolerance and that vitamin D analogs conserve immunomodulatory potential and are less toxic, we investigated the efficacy of epicutaneous application of a myelin oligodendrocyte glycoprotein peptide (MOG35-55) associated with paricalcitol (PARI) on EAE development. Three and 11 days after EAE induction, C57BL/6 mice were treated with an occlusive patch containing MOG plus PARI. Clinical parameters were daily assessed, whereas immunological and histological evaluations were performed during the acute EAE phase. MOG and MOG + PARI significantly controlled disease development reducing weight loss and clinical score. Moreover, MOG and MOG + PARI reduced the inflammatory process and preserved the myelin sheath in the CNS. High percentages of Foxp3+ regulatory T cells (Tregs) and lower MHCII fluorescence intensity in dendritic cells in draining lymph nodes were concomitantly observed. MOG + PARI association was, however, more efficient being able to reduce disease incidence and clinical scores more significantly than MOG or PARI alone. This experimental group also displayed a higher ratio between mRNA expression for Foxp3 and RORc and a higher percentage of Foxp3+ cells in the CNS. Modulation of activation markers observed in microglial cells eluted from EAE treated mice were confirmed by in vitro studies with the BV-2 microglial cell line. The results show that MOG + PARI association applied by an epicutaneous route controlled EAE development. Protective involved mechanisms include mainly a higher proportion of Tregs and also a direct immunomodulatory effect of PARI on microglial cells.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Microbiology and Immunology Institute of Biosciences São Paulo State University (UNESP)Department of Microbiology and Immunology Institute of Biosciences São Paulo State University (UNESP)FAPESP: 2013/26257-8Universidade Estadual Paulista (Unesp)Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]Mimura, Luiza Ayumi Nishiyama [UNESP]Fraga-Silva, Thais Fernanda Campos [UNESP]Ishikawa, Larissa Lumi Watanabe [UNESP]França, Thais Graziela Donegá [UNESP]Sartori, Alexandrina [UNESP]2018-12-11T17:15:31Z2018-12-11T17:15:31Z2017-10-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.3389/fimmu.2017.01198Frontiers in Immunology, v. 8, n. OCT, 2017.1664-3224http://hdl.handle.net/11449/17536610.3389/fimmu.2017.011982-s2.0-850318252982-s2.0-85031825298.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Immunology2,803info:eu-repo/semantics/openAccess2023-10-14T06:04:01Zoai:repositorio.unesp.br:11449/175366Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-10-14T06:04:01Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analog
title Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analog
spellingShingle Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analog
Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]
Epicutaneous route
Experimental autoimmune encephalomyelitis
MOG
Regulatory T cell
Vitamin D analog
title_short Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analog
title_full Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analog
title_fullStr Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analog
title_full_unstemmed Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analog
title_sort Experimental autoimmune encephalomyelitis is successfully controlled by epicutaneous administration of MOG plus vitamin D analog
author Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]
author_facet Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]
Mimura, Luiza Ayumi Nishiyama [UNESP]
Fraga-Silva, Thais Fernanda Campos [UNESP]
Ishikawa, Larissa Lumi Watanabe [UNESP]
França, Thais Graziela Donegá [UNESP]
Sartori, Alexandrina [UNESP]
author_role author
author2 Mimura, Luiza Ayumi Nishiyama [UNESP]
Fraga-Silva, Thais Fernanda Campos [UNESP]
Ishikawa, Larissa Lumi Watanabe [UNESP]
França, Thais Graziela Donegá [UNESP]
Sartori, Alexandrina [UNESP]
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]
Mimura, Luiza Ayumi Nishiyama [UNESP]
Fraga-Silva, Thais Fernanda Campos [UNESP]
Ishikawa, Larissa Lumi Watanabe [UNESP]
França, Thais Graziela Donegá [UNESP]
Sartori, Alexandrina [UNESP]
dc.subject.por.fl_str_mv Epicutaneous route
Experimental autoimmune encephalomyelitis
MOG
Regulatory T cell
Vitamin D analog
topic Epicutaneous route
Experimental autoimmune encephalomyelitis
MOG
Regulatory T cell
Vitamin D analog
description Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely employed to evaluate new strategies to control MS, including procedures to induce immunological tolerance. Considering that skin exposure to protein antigens can induce tolerance and that vitamin D analogs conserve immunomodulatory potential and are less toxic, we investigated the efficacy of epicutaneous application of a myelin oligodendrocyte glycoprotein peptide (MOG35-55) associated with paricalcitol (PARI) on EAE development. Three and 11 days after EAE induction, C57BL/6 mice were treated with an occlusive patch containing MOG plus PARI. Clinical parameters were daily assessed, whereas immunological and histological evaluations were performed during the acute EAE phase. MOG and MOG + PARI significantly controlled disease development reducing weight loss and clinical score. Moreover, MOG and MOG + PARI reduced the inflammatory process and preserved the myelin sheath in the CNS. High percentages of Foxp3+ regulatory T cells (Tregs) and lower MHCII fluorescence intensity in dendritic cells in draining lymph nodes were concomitantly observed. MOG + PARI association was, however, more efficient being able to reduce disease incidence and clinical scores more significantly than MOG or PARI alone. This experimental group also displayed a higher ratio between mRNA expression for Foxp3 and RORc and a higher percentage of Foxp3+ cells in the CNS. Modulation of activation markers observed in microglial cells eluted from EAE treated mice were confirmed by in vitro studies with the BV-2 microglial cell line. The results show that MOG + PARI association applied by an epicutaneous route controlled EAE development. Protective involved mechanisms include mainly a higher proportion of Tregs and also a direct immunomodulatory effect of PARI on microglial cells.
publishDate 2017
dc.date.none.fl_str_mv 2017-10-16
2018-12-11T17:15:31Z
2018-12-11T17:15:31Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3389/fimmu.2017.01198
Frontiers in Immunology, v. 8, n. OCT, 2017.
1664-3224
http://hdl.handle.net/11449/175366
10.3389/fimmu.2017.01198
2-s2.0-85031825298
2-s2.0-85031825298.pdf
url http://dx.doi.org/10.3389/fimmu.2017.01198
http://hdl.handle.net/11449/175366
identifier_str_mv Frontiers in Immunology, v. 8, n. OCT, 2017.
1664-3224
10.3389/fimmu.2017.01198
2-s2.0-85031825298
2-s2.0-85031825298.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Frontiers in Immunology
2,803
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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