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 1 cells develop normally in VDR knockout (KO) mice but over-produce IFN-gamma and IL-17. Naturally occurring FoxP3+ regulatory T cells are present in normal numbers in VDR 1(0 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/CD8 alpha alpha intraepithelial lymphocytes (IEL). Protective immune responses that depend on iNKT cells or CD8 alpha alpha 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. (C) 2011 Published by Elsevier Ltd.