1,25-dihydroxyvitamin D3 -induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells

Abstract

Dendritic cells (DCs), a bridge for innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D₃ and transferred the tolerogenic DCs (VD₃ -DCs) into EAE mice by adoptive transfer. We found that VD₃ -DCs inhibited the infiltrations of T helper type 1 (Th1) and Th17 cells into spinal cord and increased the proportions of regulatory T cells (CD4⁺ CD25⁺ Foxp3⁺ ), CD4⁺ IL-10⁺ T cells and regulatory B cells (CD19⁺ CD5⁺ CD1d⁺ ) in peripheral immune organs, which resulted in attenuated EAE. However, the proportions of T helper type 1 (Th1) and Th17 cells in spleen and lymph nodes and the levels of pro-inflammatory cytokines and IgG in serum also increased after transfer of VD₃ -DCs. We conclude that transfer of VD₃ -DCs suppressed EAE by increasing proportions of regulatory T cells, CD4⁺ IL-10⁺ T cells and regulatory B cells in spleen and reducing infiltration of Th1 and Th17 cells into spinal cord, which suggests a possible immunotherapy method using VD₃ -DCs in MS.

Keywords: 1,25-dihydroxyvitamin D3; experimental autoimmune encephalomyelitis; multiple sclerosis; tolerogenic dendritic cells.