PLoS ONE (Sep 2010)

1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H)17 cells to protect against experimental autoimmune encephalomyelitis.

  • Jae-Hoon Chang,
  • Hye-Ran Cha,
  • Dong-Sup Lee,
  • Kyoung Yul Seo,
  • Mi-Na Kweon

DOI
https://doi.org/10.1371/journal.pone.0012925
Journal volume & issue
Vol. 5, no. 9
p. e12925

Abstract

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BackgroundVitamin D(3), the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D(3) ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE); however, the direct effect of vitamin D(3) on T cells is largely unknown.Methodology/principal findingsIn an in vitro system using cells from mice, the active form of vitamin D(3) (1,25-dihydroxyvitamin D(3)) suppresses both interleukin (IL)-17-producing T cells (T(H)17) and regulatory T cells (Treg) differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) to reduce the amount of IL-2 regulates the generation of Treg cells, but not T(H)17 cells. Under T(H)17-polarizing conditions, 1,25(OH)(2)D(3) helps to increase the numbers of IL-10-producing T cells, but 1,25(OH)(2)D(3)'s negative regulation of T(H)17 development is still defined in the IL-10(-/-) T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH)(2)D(3) inhibits IL-17 production in STAT1(-/-) T cells. Most interestingly, 1,25(OH)(2)D(3) negatively regulates CCR6 expression which might be essential for T(H)17 cells to enter the central nervous system and initiate EAE.Conclusions/significanceOur present results in an experimental murine model suggest that 1,25(OH)(2)D(3) can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for T(H)17-mediated autoimmune diseases.