Intracellular glutathione redox status in human dendritic cells regulates IL-27 production and T-cell polarization
Intracellular glutathione redox status in human dendritic cells regulates IL-27 production and T-cell polarization
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DOI：
10.1111/j.1398-9995.2011.02611.x
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发表时间：
2011-09-01
期刊：
影响因子：
12.4
通讯作者：
Mori, M.
中科院分区：
文献类型：
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作者：
Kamide, Y.;Utsugi, M.;Mori, M.
背景：谷胱甘肽氧化还原状态，即细胞内还原型 (GSH) 或氧化型 (GSSG) 谷胱甘肽的变化，在细胞功能的各个方面发挥着重要作用。在本研究中，我们检测了人树突状细胞 (DC) 中的细胞内谷胱甘肽氧化还原状态是否调节 Th1/Th2 平衡的极化。方法：用谷胱甘肽还原型乙酯 (GSH-OEt) 或 L-丁硫氨酸-(S, R)-亚磺酰亚胺 (BSO) 处理的人单核细胞来源的 DC (MD-DC) 受到刺激 脂多糖（LPS），并测量极化细胞因子的水平。接下来，将经 LPS 或胸腺基质淋巴细胞生成素 (TSLP) 成熟的 DC 与同种异体 CD4(+) 初始 T 细胞共培养，并通过引发的 T 细胞产生的细胞因子来评估 Th1/Th2 平衡。 结果：暴露于 GSH-OEt 和 BSO 的单核细胞来源的 DC 分别增加和减少了细胞内 GSH 含量。 GSH-OEt 增强脂多糖诱导的白细胞介素 (IL)-27 的产生，BSO 抑制其产生，但 GSH-OEt 和 BSO 都不影响 HLA-DR、CD80、CD83 或 CD86 的表达。与未处理的 MD-DC 相比，成熟的 GSH-OEt 处理的 MD-DC 增强了 CD4+ T 细胞的干扰素 (IFN)-γ 产生，而针对 IL-27 的小干扰 RNA (siRNA) 抑制了 GSH-OEt 对 IFN-γ 产生的影响。此外，虽然TSLP（TSLP-DC）激活的人骨髓DC能够促使幼稚CD4（+）T细胞分化为Th2细胞，但用GSH-OEt处理TSLP-DC可减少IL-13的产生并增强CD4（+）T细胞的IFN-γ产生。 Interleukin-27 siRNA 减弱了 GSH-OEt 对 Th2 极化的抑制作用。结论：我们的结果表明，Th1 和 Th2 反应是通过 DC 中细胞内谷胱甘肽氧化还原状态通过 IL-27 的产生来控制的。
Background: Glutathione redox status, changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione, plays a significant role in various aspects of cellular function. In this study, we examined whether intracellular glutathione redox status in human dendritic cells (DCs) regulates the polarization of Th1/Th2 balance.Methods: Human monocyte-derived DCs (MD-DCs) treated with glutathione reduced form ethyl ester (GSH-OEt) or L-buthionine-(S, R)-sulfoximine (BSO) were stimulated by lipopolysaccharide (LPS), and the levels of polarization cytokines were measured. Next, DCs matured by LPS or thymic stromal lymphopoietin (TSLP) were cocultured with allogeneic CD4(+) naive T cells and Th1/Th2 balance was evaluated by cytokine production from the primed T cells.Results: Monocyte-derived DCs exposed to GSH-OEt and BSO had increased and decreased intracellular GSH contents, respectively. Lipopolysaccharide-induced interleukin (IL)-27 production was enhanced by GSH-OEt and suppressed by BSO, but neither GSH-OEt nor BSO affected the expression of HLA-DR, CD80, CD83, or CD86. Mature GSH-OEt-treated MD-DCs enhanced interferon (IFN)-gamma production from CD4(+) T cells compared with nontreated MD-DCs, and small interfering RNA (siRNA) against IL-27 suppressed the effect of GSH-OEt on IFN-gamma production. Additionally, although human myeloid DCs activated by TSLP (TSLP-DCs) prime naive CD4(+) T cells to differentiate into Th2 cells, treatment of TSLP-DCs with GSH-OEt reduced IL-13 production and enhanced IFN-gamma production by CD4(+) T cells. Interleukin-27 siRNA attenuated the inhibitory effect of GSH-OEt on Th2 polarization.Conclusion: Our results reveal that Th1 and Th2 responses are controlled by intracellular glutathione redox status in DCs through IL-27 production.