Artemisinin analogue SM934 ameliorates murine experimental autoimmune encephalomyelitis through enhancing the expansion and functions of regulatory T cell.
Artemisinin analogue SM934 ameliorates murine experimental autoimmune encephalomyelitis through enhancing the expansion and functions of regulatory T cell.
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青蒿素类似物 SM934 通过增强调节性 T 细胞的扩增和功能改善小鼠实验性自身免疫性脑脊髓炎
DOI：
10.1371/journal.pone.0074108
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zuo JP
中科院分区：
文献类型：
--
作者：
Li X;Li TT;Zhang XH;Hou LF;Yang XQ;Zhu FH;Tang W;Zuo JP
青蒿素类似物SM934先前被报道具有免疫抑制特性。本研究的目的是确定SM934在小鼠实验性自身免疫性脑脊髓炎（EAE）中的作用及其潜在机制。方法将MOG35-55免疫后的雌性C57BL/6小鼠分别给予或不给予SM934治疗，观察其临床评分及相关指标。通过ELISA、qRT-PCR、流式细胞术和BrdU掺入实验检测Th1、Th17和调节性T （Treg）细胞谱。通过细胞内染色和流式细胞术检测探讨SM934对Th1、Th17和Treg细胞分化的影响。结果体内注射SM934可明显抑制EAE的发展，抑制血清IL-17的升高。在体外，在抗原召回刺激下，sm934处理小鼠脾细胞IL-2、IFN-γ、IL-17和IL-6的产生减少，而IL-10和TGF-β的产生增加。流式细胞术和qRT-PCR结果一致显示，SM934处理显著增加了外周细胞的Treg，同时强烈抑制了Th17和Th1的反应。此外，在脊髓病变中，SM934处理显著降低了CD4+ T细胞的浸润，其中Treg细胞百分比增加，而Th17细胞百分比与载药组相比显著降低，但Th1细胞百分比未显著降低。最后，BrdU掺入和体外Treg分化实验表明，SM934处理可以直接促进Treg细胞在体内和体外的扩增。综上所述，本研究表明SM934治疗小鼠EAE疾病可能通过诱导Treg分化扩增介导。
Background Artemisinin analogue SM934 was previously reported to possess immunosuppressive properties. The aim of this study was to determine the effects and the underlying mechanisms of SM934 in murine experimental autoimmune encephalomyelitis (EAE). Methods Female C57BL/6 mice immunized with MOG35–55 were treated with or without SM934, then the clinical scores and other relevant parameters were assessed. Th1, Th17 and regulatory T (Treg) cell profiles were determined through ELISA, qRT-PCR, flow cytometry and BrdU incorporation assay. The effects of SM934 on Th1, Th17 and Treg cells differentiation were explored through intracellular staining and flow cytometry examination. Results In vivo, administration of SM934 significantly inhibited the development of EAE and suppressed the elevation of serum IL-17. Ex vivo, upon antigen-recall stimulation, IL-2, IFN-γ, IL-17 and IL-6 production were decreased, whereas IL-10 and TGF-β production were increased from the splenocytes isolated from SM934-treated mice. Consistently, both flow cytometry and qRT-PCR results showed that SM934 treatment significantly increased the Treg, while strongly suppressed the Th17 and Th1, responses in the peripheral. Furthermore, in the spinal lesion, SM934 treatment dramatically decreased the infiltration of CD4+ T cells, within which the Treg cells percentage was enlarged, whereas the Th17, but not Th1 percentage, was significantly decreased comparing with the vehicle-treated groups. Finally, both BrdU incorporation and in vitro Treg differentiation assays revealed that SM934 treatment could directly promote the expansion of Treg cells in vivo and in vitro. Conclusion Taken together, this study demonstrated that SM934 treatment could ameliorate the murine EAE disease, which might be mediated by inducing Treg differentiation and expansion.
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影响因子：
3.7
作者：
Hou LF;He SJ;Li X;Wan CP;Yang Y;Zhang XH;He PL;Zhou Y;Zhu FH;Yang YF;Li Y;Tang W;Zuo JP
通讯作者：
Zuo JP
影响因子：
4.4
作者：
Elhofy, A;Kennedy, KJ;Karpus, WJ
通讯作者：
Karpus, WJ
白介素10在抑制肠炎的调节T细胞功能中的重要作用。
影响因子：
15.3
作者：
Asseman, C;Mauze, S;Leach, M W;Coffman, R L;Powrie, F
通讯作者：
Powrie, F
影响因子：
4.4
作者：
Gondek, DC;Lu, LF;Noelle, RJ
通讯作者：
Noelle, RJ
DOI：
10.1084/jem.20080159
发表时间：
2008-07-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kroenke MA;Carlson TJ;Andjelkovic AV;Segal BM
通讯作者：
Segal BM