Vitamin D regulation of immune function in the gut: why do T cells have vitamin D receptors?

Low vitamin D status is associated with an increased risk of immune-mediated diseases like inflammatory bowel disease (IBD) in humans. Experimentally vitamin D status is a factor that shapes the immune response. Animals that are either vitamin D deficient or vitamin D receptor (VDR) deficient are prone to develop IBD. Conventional T cells develop normally in VDR knockout (KO) mice but over-produce IFN-γ and IL-17. Naturally occurring FoxP3+ regulatory T cells are present in normal numbers in VDR KO mice and function as well as wildtype T regs. Vitamin D and the VDR are required for the development and function of two regulatory populations of T cells that require non-classical MHC class 1 for development. The two vitamin D dependent cell types are the iNKT cells and CD4/CD8αα intraepithelial lymphocytes (IEL). Protective immune responses that depend on iNKT cells or CD8αα IEL are therefore impaired in the vitamin D or VDR deficient host and the mice are more susceptible to immune-mediated diseases in the gut.