Vitamin D and 1,25(OH)2D Regulation of T Cells

Nutrients. 2015 Apr 22;7(4):3011-21. doi: 10.3390/nu7043011.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Ergocalciferols / pharmacology*
  • Humans
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / metabolism
  • Interleukin-4 / metabolism
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / metabolism
  • Mice
  • Receptors, Calcitriol / metabolism
  • Receptors, Interleukin-10 / metabolism
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / metabolism*
  • Vitamin D / pharmacology*

Substances

  • Ergocalciferols
  • Interleukin-17
  • Receptors, Calcitriol
  • Receptors, Interleukin-10
  • Interleukin-10
  • Vitamin D
  • Interleukin-4
  • 1,25-dihydroxyergocalciferol
  • Interferon-gamma