Chang JH, Cha HR, Lee DS et al.1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H)17 cells to protect against experimental autoimmune encephalomyelitis. PloS ONE 5:e12925

Mucosal Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul, Korea.
PLoS ONE (Impact Factor: 3.23). 12/2010; 5(9):e12925. DOI: 10.1371/journal.pone.0012925
Source: PubMed


Vitamin 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.
In 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.
Our 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.

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Available from: Jae-Hoon Chang
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    • "Finally, we examined the role of vitamin A and D in regulating the generation of Th17 cells. Both ATRA and 1,25D3 have been shown to suppress Th17 generation via downregulation of RARa and the transcriptional factor RORc, which orchestrates Th17 differentiation (Mucida et al., 2007; Chang et al., 2010; Ikeda et al., 2010). We found that ATRA and 1,25D3 inhibited IL-17 mRNA and protein expression in response to stimulation with P. acnes. "
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    • "Preclinical studies have shown that 1,25(OH)2D3 treatment effectively ameliorated EAE in mice [6], [7], [8], [9], [10], [11]. However, the mechanism by which this hormone provides the therapeutic effects has not been fully understood. "
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    • "In fact, several groups have established that 1,25-(OH) 2 D 3 inhibits both T H 1 and T H 17 cell differentiation in vitro (Mattner et al., 2000; Chang et al., 2010a). Using the EAE model, in vivo use of 1,25-(OH) 2 D 3 (3 mg/kg) inhibited both T H 1 and T H 17 mediated disease induction, as evidenced by decreased inflammatory infiltration and reduced demyelination of the brain and spinal cord (Mattner et al., 2000; Chang et al., 2010a). In addition, 1,25-(OH) 2 D 3 has been shown to inhibit macrophage accumulation in the CNS during EAE development; thus, 1,25-(OH) 2 D 3 is acting on various cell types, leading to the protective effects seen after administration of vitamin D 3 (Nashold et al., 2000). "
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