1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H)17 cells to protect against experimental autoimmune encephalomyelitis.
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.


RESULTS
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.


CONCLUSIONS
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.
Chang
Jae-Hoon
JH
Mucosal Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul, Korea.
Cha
Hye-Ran
HR
Lee
Dong-Sup
DS
Seo
Kyoung Yul
KY
Kweon
Mi-Na
MN
D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D020011:Protective Agents / Q000008:administration & dosage*; D058504:Th17 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D007376:Interleukin-2; D020011:Protective Agents; D002117:Calcitriol