1,25-dihydroxyvitamin D3 inhibits the differentiation and migration of TH17 cells to protect against experimental autoimmune encephalomyelitis

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

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Background: Vitamin D3, 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 D3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE); however, the direct effect of vitamin D3 on T cells is largely unknown. Methodology/Principal Findings: In an in vitro system using cells from mice, the active form of vitamin D3 (1,25-dihydroxyvitamin D3) suppresses both interleukin (IL)-17-producing T cells (TH17) and regulatory T cells (Treg) differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to reduce the amount of IL-2 regulates the generation of Treg cells, but not TH17 cells. Under TH17-polarizing conditions, 1,25(OH)2D3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH)2D3's negative regulation of TH17 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)2D3 inhibits IL-17 production in STAT1-/- T cells. Most interestingly, 1,25(OH)2D3 negatively regulates CCR6 expression which might be essential for TH17 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)2D3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for TH17-mediated autoimmune diseases.

Original languageEnglish
Article numbere12925
JournalPloS one
Volume5
Issue number9
DOIs
Publication statusPublished - 2010 Nov 1

Fingerprint

Th17 Cells
calcitriol
T-cells
Autoimmune Experimental Encephalomyelitis
Calcitriol
encephalitis
cell movement
T-lymphocytes
Cholecalciferol
T-Lymphocytes
cholecalciferol
Interleukin-17
Interleukin-10
interleukin-10
Regulatory T-Lymphocytes
vitamin D
Cell Differentiation
cell differentiation
Calcitriol Receptors
cells

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "1,25-dihydroxyvitamin D3 inhibits the differentiation and migration of TH17 cells to protect against experimental autoimmune encephalomyelitis",
abstract = "Background: Vitamin D3, 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 D3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE); however, the direct effect of vitamin D3 on T cells is largely unknown. Methodology/Principal Findings: In an in vitro system using cells from mice, the active form of vitamin D3 (1,25-dihydroxyvitamin D3) suppresses both interleukin (IL)-17-producing T cells (TH17) and regulatory T cells (Treg) differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to reduce the amount of IL-2 regulates the generation of Treg cells, but not TH17 cells. Under TH17-polarizing conditions, 1,25(OH)2D3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH)2D3's negative regulation of TH17 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)2D3 inhibits IL-17 production in STAT1-/- T cells. Most interestingly, 1,25(OH)2D3 negatively regulates CCR6 expression which might be essential for TH17 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)2D3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for TH17-mediated autoimmune diseases.",
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1,25-dihydroxyvitamin D3 inhibits the differentiation and migration of TH17 cells to protect against experimental autoimmune encephalomyelitis. / Chang, Jae Hoon; Cha, Hye Ran; Lee, Dong Sup; Seo, Kyoung Yul; Kweon, Mi Na.

In: PloS one, Vol. 5, No. 9, e12925, 01.11.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 1,25-dihydroxyvitamin D3 inhibits the differentiation and migration of TH17 cells to protect against experimental autoimmune encephalomyelitis

AU - Chang, Jae Hoon

AU - Cha, Hye Ran

AU - Lee, Dong Sup

AU - Seo, Kyoung Yul

AU - Kweon, Mi Na

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Y1 - 2010/11/1

N2 - Background: Vitamin D3, 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 D3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE); however, the direct effect of vitamin D3 on T cells is largely unknown. Methodology/Principal Findings: In an in vitro system using cells from mice, the active form of vitamin D3 (1,25-dihydroxyvitamin D3) suppresses both interleukin (IL)-17-producing T cells (TH17) and regulatory T cells (Treg) differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to reduce the amount of IL-2 regulates the generation of Treg cells, but not TH17 cells. Under TH17-polarizing conditions, 1,25(OH)2D3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH)2D3's negative regulation of TH17 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)2D3 inhibits IL-17 production in STAT1-/- T cells. Most interestingly, 1,25(OH)2D3 negatively regulates CCR6 expression which might be essential for TH17 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)2D3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for TH17-mediated autoimmune diseases.

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