期刊
MOLECULAR IMMUNOLOGY
卷 91, 期 -, 页码 156-164出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2017.09.006
关键词
1,25(OH)(2)D-3; Treg/Th17 cells; VDR /PLC-gamma 1/TGF-beta 1 pathway
资金
- project of Medical Professionals Cross Fund, Shanghai Jiao Tong University, Shanghai, China [YG2013MS01]
- 863 Program [2012AA02A515, 2012AA021802]
- National Nature Science Foundation of China [81421061, 81273596, J1210047, 30900799, 81361120389, 30972823]
- National key research and development program [2016YFC0905000, 2016YFC1200200, 2016YFC0906400]
- 4th Three-year Action Plan for Public Health of Shanghai [15GWZK0101]
- Shanghai Key Laboratory of Psychotic Disorders [13dz2260500]
- Public Science and Technology Research Funds [201210056]
Vitamin D has been recommended as an immune modulator in recent years, in addition to regulating calcium-phosphorous-bone metabolism. Clinical studies on organ transplantation found that vitamin D sufficiency patients were less likely to develop acute cellular rejection within one year after transplantation compared to those with vitamin D deficiency. Thus, a high percentage of regulatory T cells might play a key role in preventing acute cellular rejection (ACR). In this report, we studied the specific effects of 1,25(OH)(2)D-3 on human T cell differentiation, and determined the potential molecule mechanism behind. Results showed that 1,25(OH)(2)D-3 induced the differentiation of T-regulatory cells (Treg cells), while inhibiting Th17 cell proliferation. In addition, 1,25(OH)(2)D-3 promoted secretion of the anti-inflammatory cytokine, transforming Growth Factor beta1 (TGF-beta 1) but suppressed pro-inflammatory cytokines such as interleukin17 (IL-17). Phospholipase C gamma 1 (PLC-gamma 1) is an indispensable signaling protein downstream of the classical TCR signaling pathway and was shown to play a crucial role in T cell activation, while Naive T cells expressed less PLC-gamma 1. Here we showed that Vitamin D could significantly upregulate PLC-gamma 1 expression, which then induced expression of TGF-beta 1. In summary, 1,25(OH)(2)D-3 indirectly modulates the differentiation of Treg/Th17 cells by aff;ecting the VDR/PLC-gamma 1/TGF-beta 1 pathway. These results indicate that administration 1,25(OH)(2)D-3 supplements may be a beneficial treatment for organ transplantation recipients.
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