Total glucosides of paeony induces regulatory CD4+CD25+ T cells by increasing Foxp3 demethylation in lupus CD4+ T cells

Total glucosides of paeony induces regulatory CD4+CD25+ T cells by increasing Foxp3 demethylation in lupus CD4+ T cells
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DOI:
10.1016/j.clim.2012.02.002
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发表时间:
2012-05-01
影响因子:
8.6
通讯作者:
Lu, Qian-jin
Lu, Qian-jin
中科院分区:
医学3区
文献类型:
--
作者:
Zhao, Ming;Liang, Gong-ping;Lu, Qian-jin

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白芍总苷(TGP)是从白芍中提取的有效成分,已被用于治疗自身免疫性疾病。然而,TGP预防自身免疫反应的分子机制尚不清楚。在这项研究中,我们发现TGP治疗显著增加了狼疮CD 4(+)T细胞中Treg细胞的百分比和数量。进一步的研究表明,TGP治疗通过下调Foxp 3启动子甲基化水平增加了狼疮CD 4(+)T细胞中Foxp 3的表达。然而,我们不能观察到类似的结果,在健康对照组的CD 4(+)T细胞TGP处理。此外,我们的研究结果还表明,IFN-γ和IL-2的表达增强TGP处理的狼疮CD 4(+)T细胞。这些发现表明TGP可能通过诱导Treg细胞分化来抑制SLE患者的自身免疫,这可能是由于其能够调节Foxp 3启动子的甲基化状态并激活IFN-γ和IL-2信号传导。(C)2012 Elsevier Inc. All rights reserved.
Total glucosides of paeony (TGP), an active compound extracted from Paeony root, has been used in therapy for autoimmune diseases. However the molecular mechanism of TGP in the prevention of autoimmune response remains unclear. In this study, we found that TGP treatment significantly increased the percentage and number of Treg cells in lupus CD4(+) T cells. Further investigation revealed that treatment with TGP increased the expression of Foxp3 in lupus CD4(+) T cells by down-regulating Foxp3 promoter methylation levels. However, we couldn't observe similar results in healthy control CD4(+) T cells treated by TGP. Moreover, our results also showed that IFN-gamma and IL-2 expression was enhanced in TGP-treated lupus CD4(+) T cells. These findings indicate that TGP inhibits autoimmunity in SLE patients possibly by inducing Treg cell differentiation, which may in turn be due to its ability to regulate the methylation status of the Foxp3 promoter and activate IFNI-gamma and IL-2 signaling. (C) 2012 Elsevier Inc. All rights reserved.