Open AccessVitamin D 3 Induces IDO + Tolerogenic DC s and Enhances Treg, Reducing the Severity of EAE
Author(s) -
Farias Alessandro S.,
Spagnol Gabriela S.,
BordeauxRego Pedro,
Oliveira Camila O.F.,
Fontana Ana Gabriela M.,
Paula Rosemeire F.O.,
Santos Mariana P.A.,
Pradella Fernando,
Moraes Adriel S.,
Oliveira Elaine C.,
Longhini Ana Leda F.,
Rezende Alexandre C.S.,
Vaisberg Mauro W.,
Santos Leonilda M.B.
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12071
Subject(s) - experimental autoimmune encephalomyelitis , foxp3 , adoptive cell transfer , immunology , il 2 receptor , medicine , vitamin d and neurology , cd80 , immune tolerance , interleukin 10 , regulatory t cell , t cell , population , immune system , biology , cytotoxic t cell , endocrinology , cd40 , in vitro , biochemistry , environmental health
Summary 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 DC s generated in the presence of vitamin D3. Results This study provides evidence that the in vivo administration of vitamin D 3, as well as the adoptive transfer of vitamin D 3 ‐induced IDO + immature/tolerogenic dendritic cells, leads to a significant increase in the percentage of CD 4 + CD 25 + 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 DC s cultivated in the presence of vitamin D 3 present a tolerogenic profile with high IL ‐10, TNF α, and IDO expression and decreased MHC ‐ II and CD 80 expression. The adoptive transfer of IDO + DC s induces a significant increase in the percentage of CD 4 + CD 25 + Foxp3 + T cells in the lymph nodes, comparable with vitamin D 3 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.