Abstract
Vitamin D is a direct and indirect regulator of T cells. The mechanisms by which vitamin D directly regulates T cells are reviewed and new primary data on the effects of 1,25 dihydroxyvitamin D (1,25(OH)2D) on human invariant natural killer (iNK)T cells is presented. The in vivo effects of vitamin D on murine T cells include inhibition of T cell proliferation, inhibition of IFN-γ, IL-17 and induction of IL-4. Experiments in mice demonstrate that the effectiveness of 1,25(OH)2D requires NKT cells, IL-10, the IL-10R and IL-4. Comparisons of mouse and human T cells show that 1,25(OH)2D inhibits IL-17 and IFN-γ, and induces T regulatory cells and IL-4. IL-4 was induced by 1,25(OH)2D in mouse and human iNKT cells. Activation for 72h was required for optimal expression of the vitamin D receptor (VDR) in human and mouse T and iNKT cells. In addition, T cells are potential autocrine sources of 1,25(OH)2D but again only 48–72h after activation. Together the data support the late effects of vitamin D on diseases like inflammatory bowel disease and multiple sclerosis where reducing IL-17 and IFN-γ, while inducing IL-4 and IL-10, would be beneficial.
Highlights
Vitamin D is a fat soluble vitamin that is either consumed in the diet or produced in the skin following sunlight exposure of the skin
The classic roles of vitamin D are in the regulation of calcium uptake and homeostasis, bone metabolism, and cell growth and division
Vitamin D controls CD8 proliferation, IL-2 production and the potential to develop into effector T cells that produce IFN-γ, IL-17 and granzyme B
Summary
Vitamin D is a fat soluble vitamin that is either consumed in the diet or produced in the skin following sunlight exposure of the skin. Vitamin D is inactive and is hydroxylated twice, once in the liver and once in the kidney to make the active form of the vitamin, 1,25 dihydroxyvitamin D (1,25(OH)2D) [1,2]. Production of 1,25(OH)2D in the kidney is tightly regulated by serum calcium, parathyroid hormone and. Vitamin D as 1,25(OH)2D functions by binding to a nuclear vitamin D receptor (VDR) and retinoid X receptor to regulate gene transcription [4]. The classic roles of vitamin D are in the regulation of calcium uptake and homeostasis, bone metabolism, and cell growth and division. The. 1,25(OH)2D and vitamin D are important immune system regulators [5]. All cells of the immune system have been shown to express the VDR including T cells [6]
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