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白芍总苷通过增加狼疮 CD4+T 细胞中 Foxp3 的去甲基化诱导调节性 CD4+CD25+T 细胞。

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

机构信息

Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.

出版信息

Clin Immunol. 2012 May;143(2):180-7. doi: 10.1016/j.clim.2012.02.002. Epub 2012 Feb 16.

DOI:10.1016/j.clim.2012.02.002
PMID:22406048
Abstract

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-γ 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 IFN-γ and IL-2 signaling.

摘要

白芍总苷(TGP)是从芍药根中提取的一种活性化合物,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 治疗可显著增加狼疮 CD4(+)T 细胞中 Treg 细胞的百分比和数量。进一步的研究表明,TGP 通过下调 Foxp3 启动子甲基化水平来增加狼疮 CD4(+)T 细胞中 Foxp3 的表达。然而,我们在 TGP 处理的健康对照 CD4(+)T 细胞中未观察到类似结果。此外,我们的结果还表明,IFN-γ 和 IL-2 的表达在 TGP 处理的狼疮 CD4(+)T 细胞中增强。这些发现表明,TGP 通过诱导 Treg 细胞分化来抑制 SLE 患者的自身免疫,这可能是由于其调节 Foxp3 启动子甲基化状态和激活 IFN-γ 和 IL-2 信号的能力。

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