1,25(OH)2D3 induces regulatory T cell differentiation by influencing the VDR/PLC-γ1/TGF-β1/pathway

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.