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)(2)D(3)) suppresses the development of animal models of human autoimmune diseases. 1,25(OH)(2)D(3) decreased the proliferation of all T helper (h) cells and decreased the production of IFN-gamma, IL-2, and IL-5. In Th2 cells 1,25(OH)(2)D(3) 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)(2)D(3) 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)(2)D(3) in CD4+ T cells. Of the 102 genes, 57 genes were down-regulated and 45 were up-regulated by 1,25(OH)(2)D(3) treatment of the CD4+ T cells. Two of the identified genes are regulators of NFkB. Other genes of interest included the IL-2Rbeta gene and IgE binding factor. Th2 and Th0 cells produced more IgE binding factor after treatment with 1,25(OH)(2)D(3) while Th1 cell IgE binding factor expression was unaffected by 1,25(OH)(2)D(3) addition. It is unclear why some of the genes identified are expressed in CD4+ T cells and furthermore why 1,25(OH)(2)D(3) 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.
Mahon
Brett D
BD
Department of Nutrition, The Pennsylvania State University, University Park, PA 16802, USA.
Wittke
Anja
A
Weaver
Veronika
V
Cantorna
Margherita T
MT
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018167:Receptors, Calcitriol / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D004268:DNA-Binding Proteins; D007378:Interleukins; D018167:Receptors, Calcitriol; D011971:Receptors, Immunologic; D015759:Ionomycin; D007371:Interferon-gamma; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate