Vitamin D down-regulates the expression of some Th17 cell-related cytokines, key inflammatory chemokines, and chemokine receptors in experimental autoimmune encephalomyelitis

Abstract

VD down-regulates the expression of some inflammatory cytokines, chemokines and chemokine receptors in EAE mice. The possible therapeutic potential of VD in multiple sclerosis can be considered in future investigation.

The role of chemokines and chemokine receptors in multiple sclerosis

“…It is further supposed that exposure to pathogens early in life might result in the production of CCL20 by autoantibodies and trigger a protective effect against MS development [1]. In the research of Jafarzadeh A et al, the CCL20 and CCR6 expression levels in the spinal cord of EAE mice (MOG induced in C57BL/6J mice) administered with PBS were evidently elevated compared to the control group [43,44].…”

“…CCL22 is a chemokine for the accumulation and movement of CCR4expressing cells (contains Th2/Treg cells) into the site of inflammation [44] and can be produced by microglia and astrocytes [81]. Macrophage-derived chemokines (CCL22) are produced by monocyte-derived dendritic cells and macrophages upon stimulation with anti-CD40 antibodies or microbial products and are downregulated by Th1 type cytokines, but upregulated by Th2 type cytokines [46].…”

“…CCL22 may primarily attract Treg cells, shutting down the adaptive immune response effectively [20]. The expression levels of CCR4 and CCL22 in the spinal cord of EAE mice(MOG induced in C57BL/6J mice) were significantly increased [43,44]. CCL22 expression is related to increased severity of EAE, and anti-CCL22 treatment may improve EAE development, possibly by regulating inflammatory macrophage accumulation [28].…”

“…CCR4 is mainly expressed on Th2 / Treg lymphocytes [44].CCR4 antagonists are classified into two categories of aryl sulphonamides lipophilic and heteroarenes [108]. Small molecule antagonists, like endogenous ligands, have also shown different ability to induce receptor internalization, which may be relevant to different biological effects.…”

“…Classically studied animal models of MS are (1) allergic encephalomyelitis/experimental autoimmune (EAE); (2) virus-induced models and (3) toxin-induced demyelination models [90].Experimental autoimmune encephalomyelitis (abbreviated as EAE), an experimental animal model of human MS, is obtained by using myelin oligodendrocyte protein(MOG), proteolipid protein(PLP) or myelin basic protein (MBP) immuning and inducing in certain susceptible experimental animals such as mice and other rodents [44]. Besides, EAE can be triggered by the adoptive transfer of myelin antigen-specific T cells, CD8 + T lymphocytes and Th1 and Th17 type CD4 + cells [66,87].…”