1,25-Dihydroxyvitamin D3 Inhibits the Differentiation and Migration of TH17 Cells to Protect against Experimental Autoimmune Encephalomyelitis

• Published in: PloS one Vol. 5; no. 9; p. e12925
• Main Authors: Chang, Jae-Hoon, Cha, Hye-Ran, Lee, Dong-Sup, Seo, Kyoung Yul, Kweon, Mi-Na
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 23.09.2010
• Subjects: Animal models; Autoimmune diseases; Calcitriol; CCR6 protein; Cell differentiation; Cell migration; Central nervous system; Chemokines; Cytokines; Differentiation (biology); Dihydroxyvitamin D3; Experimental allergic encephalomyelitis; Growth factors; Helper cells; Immune response; Immunology; Immunology/Autoimmunity; Immunology/Immune Response; Immunology/Leukocyte Development; Immunoregulation; Interleukin; Interleukin 10; Interleukin 17; Interleukin 2; Laboratories; Leukocyte migration; Lymphocytes; Lymphocytes T; Medical research; Multiple sclerosis; Organic compounds; Paralysis; Rheumatoid arthritis; Rodents; Science; Spinal cord; Spleen; Stat1 protein; Studies; Vitamin D; Vitamin D3
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012925

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.