Vitamin D-3 Induces IDO+ Tolerogenic DCs and Enhances Treg, Reducing the Severity of EAE

Vitamin D-3 Induces IDO+ Tolerogenic DCs and Enhances Treg, Reducing the Severity of EAE

Autor Farias, Alessandro S. Google Scholar
Spagnol, Gabriela S. Google Scholar
Bordeaux-Rego, Pedro Google Scholar
Oliveira, Camila O. F. Google Scholar
Fontana, Ana Gabriela M. Google Scholar
Paula, Rosemeire F. O. de Google Scholar
Santos, Mariana P. A. Google Scholar
Pradella, Fernando Google Scholar
Moraes, Adriel S. Google Scholar
Oliveira, Elaine C. Google Scholar
Longhini, Ana Leda F. Google Scholar
Rezende, Alexandre C. S. Google Scholar
Vaisberg, Mauro W. Autor UNIFESP Google Scholar
Santos, Leonilda M. B. Google Scholar
Instituição Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
Resumo Background A growing body of evidence supports the hypothesis that vitamin D is an important environmental factor in the etiology of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS). Aim the purpose of this study was exploring the mechanisms underlying the beneficial effect of vitamin D3 in encephalomyelitis (EAE). Methods We treated monophasic experimental autoimmune EAE, induced in Lewis rat, with vitamin D3 and adoptively transfer tolerogenic bone marrow-derived DCs generated in the presence of vitamin D3. Results This study provides evidence that the in vivo administration of vitamin D3, as well as the adoptive transfer of vitamin D3-induced IDO+ immature/tolerogenic dendritic cells, leads to a significant increase in the percentage of CD4+CD25+Foxp3+ regulatory T cells in the lymph nodes in a rat model of MS, experimental autoimmune EAE. Concomitant with the increase in this cell population, there is a significant decrease in the number of autoreactive T cells in the central nervous system. Bone marrow-derived DCs cultivated in the presence of vitamin D3 present a tolerogenic profile with high IL-10, TNF, and IDO expression and decreased MHC-II and CD80 expression. the adoptive transfer of IDO + DCs induces a significant increase in the percentage of CD4+CD25+Foxp3+ T cells in the lymph nodes, comparable with vitamin D3 treatment. Conclusion These mechanisms contribute actively to the generation of a microenvironment in the lymph nodes that suppresses the activation of encephalitogenic T cells, resulting in the downregulation of the inflammatory response in the central nervous system.
Palavra-chave Autoimmunity
DCs
T-cell activation
Tregs
Vitamin D3
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
FA-EPex UNICAMP
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
PIBIC
Número do financiamento FAPESP: 2011/18728-5
FAPESP: 2012/01408-0
FAPESP: 2011/15175-5
FAPESP: 2011/15639-1
CNPq: 290089/2004-2
Data de publicação 2013-04-01
Publicado em Cns Neuroscience & Therapeutics. Hoboken: Wiley-Blackwell, v. 19, n. 4, p. 269-277, 2013.
ISSN 1755-5930 (Sherpa/Romeo, fator de impacto)
Publicador Wiley-Blackwell
Extensão 269-277
Fonte http://dx.doi.org/10.1111/cns.12071
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000316754000009
Endereço permanente http://repositorio.unifesp.br/handle/11600/36117

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