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: 3.53). 12/2010; 5(9):e12925. DOI: 10.1371/journal.pone.0012925
Source: PubMed

ABSTRACT 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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    • "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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    ABSTRACT: Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from the immune response targeting Propionibacterium acnes plays a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of Th17 and Th1, but not Th2 responses in human PBMCs. P. acnes stimulated expression of key Th17-related genes, including IL-17A, RORα, RORc, IL-17RA and IL-17RC, and triggered IL-17 secretion from CD4(+), but not CD8(+) T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naïve CD4(+)CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6 and TGF-β neutralizing antibodies completely inhibited P. acnes-induced IL-17 production. Importantly, we showed that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors. Finally, vitamin A (all-trans retinoic acid) and vitamin D (1,25-dihydroxyvitamin D3) inhibited P. acnes-induced Th17 differentiation. Together, our data demonstrate that IL-17 is induced by P. acnes and expressed in acne lesions and that both vitamin A and vitamin D could be effective tools to modulate Th17-mediated diseases such as acne.Journal of Investigative Dermatology accepted article preview online, 7 August 2013. doi:10.1038/jid.2013.334.
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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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