期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 2, 页码 997-1004出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.163790
关键词
-
资金
- National Institutes of Health [AI035783, AI057956, DK064400]
- Crohn's and Colitis Foundation of America
- [AR053458]
Vitamin D deficiency is implicated in autoimmune disease. We therefore evaluated the effects of 1 alpha,25-dihydroxyvitamin D-3 (1,25-D-3), the active form of vitamin D, on the development of T helper 1 (Th1), Th17, and Th9 cells, which are implicated in the pathogenesis of different types of autoimmunity. 1,25-D-3 compromised the development of Th17 and Th9 cells, including IL-22-expressing cells while simultaneously increasing the frequency of IL-10-competent cells. Relative to Th17 and Th9 cells, the effects of 1,25-D-3 on Th1 cells were modest, reflecting the significantly reduced levels of the receptor for vitamin D in this lineage. The use of cells deficient in IL-10 or antibodies that block IL-10 signaling abolished the inhibitory effect of 1,25-D-3 on Th9 cells but had no effect on inhibition of Th17 cell frequencies. Thus, the induction of IL-10 in cultures of Th9 cells is an important mechanism by which 1,25-D-3 compromises Th9 development but does not explain inhibition of Th17 cells. A survey of select representatives of the Th17 transcriptome revealed that the levels of mRNA that encode ROR gamma t, IL-17A, IL-17F, IL-23R, and IL-22, were reduced by 1,25-D-3, whereas IL-21 and aryl hydrocarbon receptor mRNA remained unchanged. These data suggest that vitamin D deficiency may promote autoimmunity by favoring the inordinate production of Th17 and Th9 cells at the expense of regulatory IL-10-producing T cells.
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