1,25-Dihydroxyvitamin D-3 Inhibits the Differentiation and Migration of T(H)17 Cells to Protect against Experimental Autoimmune Encephalomyelitis

Title
1,25-Dihydroxyvitamin D-3 Inhibits the Differentiation and Migration of T(H)17 Cells to Protect against Experimental Autoimmune Encephalomyelitis
Author(s)
장재훈Hye-Ran Cha[Hye-Ran Cha]Dong-Sup Lee[Dong-Sup Lee]Kyuong Yul Seo[Kyuong Yul Seo]Mi-Na Kweon[Mi-Na Kweon]
Keywords
REGULATORY T-CELLS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; VITAMIN-D; DENDRITIC CELLS; TH17 CELLS; IN-VITRO; TGF-BETA; TRANSCRIPTIONAL REPRESSION; PREFERENTIAL RECRUITMENT
Issue Date
201009
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.5, no.9
Abstract
Background: 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. Methodology/ Principal Findings: In an in vitro system using cells from mice, the active form of vitamin D-3 (1,25dihydroxyvitamin 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 2/ 2 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 2/ 2 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/ Significance: 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.
URI
http://hdl.handle.net/YU.REPOSITORY/23685http://dx.doi.org/10.1371/journal.pone.0012925
ISSN
1932-6203
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약학대학 > 약학부 > Articles
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