Mechanisms underlying the effect of vitamin D on the immune system.

Vitamin D and the vitamin D receptor (VDR) have been shown to be important regulators of the immune system. In particular, vitamin D and VDR deficiency exacerbates experimental autoimmune diseases such as inflammatory bowel disease (IBD). IBD develops due to an immune-mediated attack by pathogenic T-cells that overproduce IL-17 and IFN-gamma and a few regulatory cells. VDR knockout mice have twice as many T-cells making IL-17 and IFN-gamma than wild-type mice. In addition, vitamin D and the VDR are required for normal numbers of regulatory T-cells (iNKT and CD8alphaalpha) that have been shown to suppress experimental IBD. In the absence of vitamin D and the VDR, autoimmunity occurs in the gastrointestinal tract due to increased numbers of IL-17 and IFN-gamma secreting T-cells and a concomitant reduction in regulatory T-cells.