The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells

Vitamin D is a potent immune system regulator. The active form of vitamin D (1,25(OH)₂D₃) suppresses the development of animal models of human autoimmune diseases. 1,25(OH)₂D₃ decreased the proliferation of all T helper (h) cells and decreased the production of IFN-γ, IL-2, and IL-5. In Th2 cells 1,25(OH)₂D₃ increased the production of IL-4. Quiescent CD4+ T cells express vitamin D receptors but only at a low level, which increased five-fold following activation. 1,25(OH)₂D₃ treatment of Th0 cells, but not Th1 or Th2 cells, induced the expression of the transcription factor GATA-3. Microarray technology identified over 102 targets of 1,25(OH)₂D₃ in CD4+ T cells. Of the 102 genes, 57 genes were down-regulated and 45 were up-regulated by 1,25(OH)₂D₃ treatment of the CD4+ T cells. Two of the identified genes are regulators of NFkB. Other genes of interest included the IL-2Rβ gene and IgE binding factor. Th2 and Th0 cells produced more IgE binding factor after treatment with 1,25(OH)₂D₃ while Th1 cell IgE binding factor expression was unaffected by 1,25(OH)₂D₃ addition. It is unclear why some of the genes identified are expressed in CD4+ T cells and furthermore why 1,25(OH)₂D₃ regulates the expression of these genes. Clearly CD4+ T cells can be direct targets of vitamin D. The targets of vitamin D in CD4+ T cells depend on the state of activation and differentiation status of the cells.