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Human placenta derived mesenchymal stromal cells alleviate GVHD by promoting the generation of GSH and GST in PD-1+T cells.
Cellular Immunology ( IF 4.3 ) Pub Date : 2020-02-28 , DOI: 10.1016/j.cellimm.2020.104083
Wang Zhuoya 1 , Zhao Nannan 1 , Zhang Aiping 1 , Wang Guoyan 2 , Dong Menghua 3 , Zhang Jiashen 1 , Xiong Yanlian 4 , Luan Xiying 1
Affiliation  

AIMS To investigate whether placenta-derived mesenchymal stromal cells (hPMSCs) have immunoregulatory effects on PD-1+ T cell generation by controlling ROS production and thus alleviating GVHD. MAIN METHODS Flow cytometry was used to analyze the percentage of PD-1+ T cells, as well as the generation of ROS, GSH and GST in PD-1+ T cells. The expression of GST in the spleen and liver was analyzed by western blotting. KEY FINDINGS The percentage of PD-1+ T cells was increased, but the ratio of GSH/GSSG was decreased in GVHD patients and the GVHDhigh mouse model compared with that in the normal control group. hPMSCs downregulated the level of malondialdehyde (MDA) and upregulated the ratio of GSH/GSSG and the expression of glutathione S transferase (GST) in the plasma, spleen and liver of GVHD mice compared with those of PBS-treated GVHD mice. Further studies showed that the ROS level, as well as the expression of PD-1, in both CD3+ and CD4+ T cells from the spleen and liver of hPMSC-treated GVHD mice were decreased compared with those observed in PBS-treated mice. SIGNIFICANCE hPMSCs downregulated ROS generation by increasing GSH and GST levels and further reduced the expression of PD-1 on T cells, thereby alleviating inflammation in GVHD mice.

中文翻译:

人胎盘来源的间充质基质细胞通过促进PD-1 + T细胞中GSH和GST的生成来减轻GVHD。

目的探讨胎盘来源的间充质基质细胞(hPMSCs)是否通过控制ROS的产生从而减轻GVHD对PD-1 + T细胞的产生具有免疫调节作用。主要方法流式细胞仪用于分析PD-1 + T细胞的百分比,以及PD-1 + T细胞中ROS,GSH和GST的生成。通过蛋白质印迹分析脾脏和肝脏中GST的表达。主要发现与正常对照组相比,GVHD患者和GVHDhigh小鼠模型中PD-1 + T细胞的百分比增加,但GSH / GSSG的比例降低。与PBS处理的GVHD小鼠相比,hPMSCs下调了GVHD小鼠血浆,脾脏和肝脏中的丙二醛(MDA)水平,并上调了GSH / GSSG的比例和谷胱甘肽S转移酶(GST)的表达。进一步的研究表明,与在PBS处理的小鼠中观察到的相比,在hPMSC处理的GVHD小鼠的脾脏和肝脏中CD3 +和CD4 + T细胞中的ROS水平以及PD-1的表达均降低了。意义hPMSC通过增加GSH和GST水平来下调ROS的产生,并进一步降低PD细胞上PD-1的表达,从而减轻GVHD小鼠的炎症。
更新日期:2020-02-28
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