Experimental Autoimmune Encephalomyelitis Is Succe... - BV FAPESP
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Experimental Autoimmune Encephalomyelitis Is Successfully Controlled by Epicutaneous Administration of MOG Plus Vitamin D Analog

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Autor(es):
Goncalves Zorzella-Pezavento, Sofia Fernanda [1] ; Nishiyama Mimura, Luiza Ayumi [1] ; Campos Fraga-Silva, Thais Fernanda [1] ; Watanabe Ishikawa, Larissa Lumi [1] ; Donega Franca, Thais Graziela [1] ; Sartori, Alexandrina [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Sao Paulo State Univ UNESP, Inst Biosci, Dept Microbiol & Immunol, Botucatu, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN IMMUNOLOGY; v. 8, OCT 16 2017.
Citações Web of Science: 1
Resumo

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 (MOG(35-55)) 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. (AU)

Processo FAPESP: 13/26257-8 - Eficácia tolerogênica da associação MOG/análogo da vitamina D ou MOG/rapamicina na encefalite autoimune experimental
Beneficiário:Alexandrina Sartori
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/01604-7 - Eficácia tolerogênica da associação MOG/análogo da vitamina D ou MOG/rapamicina na encefalite autoimune experimental
Beneficiário:Sofia Fernanda Gonçalves Zorzella Pezavento
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado