Vitamin D3 induces IDO+ tolerogenic DCs and enhances treg, reducing the severity of EAE

Abstract

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, TNFα, 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. © 2013 Blackwell Publishing Ltd.