Vitamin D and 1,25(OH)2D regulation of T cells.
Vitamin D is a direct and indirect regulator of T cells. The mechanisms by which vitamin D directly regulates T cells are reviewed and new primary data on the effects of 1,25 dihydroxyvitamin D (1,25(OH)2D) on human invariant natural killer (iNK)T cells is presented. The in vivo effects of vitamin D on murine T cells include inhibition of T cell proliferation, inhibition of IFN-γ, IL-17 and induction of IL-4. Experiments in mice demonstrate that the effectiveness of 1,25(OH)2D requires NKT cells, IL-10, the IL-10R and IL-4. Comparisons of mouse and human T cells show that 1,25(OH)2D inhibits IL-17 and IFN-γ, and induces T regulatory cells and IL-4. IL-4 was induced by 1,25(OH)2D in mouse and human iNKT cells. Activation for 72 h was required for optimal expression of the vitamin D receptor (VDR) in human and mouse T and iNKT cells. In addition, T cells are potential autocrine sources of 1,25(OH)2D but again only 48-72 h after activation. Together the data support the late effects of vitamin D on diseases like inflammatory bowel disease and multiple sclerosis where reducing IL-17 and IFN-γ, while inducing IL-4 and IL-10, would be beneficial.
Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA. mxc69@psu.edu.|Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA. mxc69@psu.edu.
Margherita T
MT
Cantorna
Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA. lms496@psu.edu.
Lindsay
L
Snyder
Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA. yxl254@psu.edu.
Yang-Ding
YD
Lin
Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA. lyang1@hmc.psu.edu.
Linlin
L
Yang
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004872:Ergocalciferols / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018167:Receptors, Calcitriol / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism*; D014807:Vitamin D / Q000494:pharmacology*
D004872:Ergocalciferols; D020381:Interleukin-17; D018167:Receptors, Calcitriol; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D014807:Vitamin D; D015847:Interleukin-4; C003564:1,25-dihydroxyergocalciferol; D007371:Interferon-gamma