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 D and transferred the tolerogenic DCs (VD -DCs) into EAE mice by adoptive transfer. We found that VD -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 VD -DCs. We conclude that transfer of VD -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 VD -DCs in MS.

Regulatory Dendritic Cells Induced by K313 Display Anti-Inflammatory Properties and Ameliorate Experimental Autoimmune Encephalitis in Mice

“…The decreased expansion of antigen-specific T cells regulated by DCregs is critical in the control of autoimmune diseases (Piemonti et al, 2000). Several studies have suggested that the inhibition of antigen-specific T cells can ameliorate disease severity in EAE mice (Serada et al, 2008;Yoshida et al, 2013;Xie et al, 2017). In this study, the co-culture experimental results confirm the conjecture that K313-modified DCregs significantly suppress the expansion of OVA 323-339 peptide-specific CD4+ T cells.…”

Generation of a novel mouse model for the study of autoimmune liver disease overlap syndrome

“…injection of tDCs was not the right way of application, although it was shown in an EAE model that i.v. injection of tDCs led to a decrease in clinical symptoms in the mice [318,319]. Another study shows that i.p.…”

Fibroblasts as an Alternative to Mesenchymal Stem Cells with Successful Treatment and Immune Modulation in EAE Model of Multiple Sclerosis

“…Mature DCs are uniquely capable of activating naïve T cells through their high and dense expression of membrane-bound costimulatory molecules such as CD40, CD80, and CD86 and the soluble costimulatory signal IL-12. Immature dendritic cells possess ability to induce immunological tolerance through their high levels of co-inhibitory molecules such as IL-10 and PD-L1 (80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94). Given that fibroblasts are associated with post-injury healing, and that upregulation of immune inhibitory molecules is known to occur in the healing phase of injury, we sought to investigate whether DC maturation was altered by fibroblasts using a co-culture system.…”