CD86
CD80
间充质干细胞
促炎细胞因子
免疫抑制
免疫学
免疫耐受
骨髓
医学
干细胞
癌症研究
细胞生物学
免疫系统
化学
CD40
T细胞
生物
炎症
体外
病理
细胞毒性T细胞
生物化学
作者
Jigang He,Beibei Li,Liang Zhou,Dan Yan,Qiao-Li Xie,Wei Zhao
出处
期刊:Journal of Investigative Medicine
[BMJ]
日期:2019-12-31
卷期号:68 (3): 728-737
被引量:21
标识
DOI:10.1136/jim-2019-001160
摘要
Expression of indoleamine 2,3-dioxygenase (IDO) in mesenchymal stem cells (MSC) is thought to contribute to MSC-mediated immunosuppression. A lentiviral-based transgenic system was used to generate bone marrow stem cells (BMSC) which stably expressed IDO (IDO-BMSCs). Coculture of IDO-BMSCs with dendritic cells (DC) or T cells was used to evaluate the immunomodulatory effect of IDO-BMSCs. A heterotopic heart transplant model in rats was used to evaluate allograft rejection after IDO-BMSC treatment. Mechanisms of IDO-BMSC-mediated immunosuppression were investigated by evaluating levels of proinflammatory and anti-inflammatory cytokines, and production of Tregs. A significant decrease in DC marker-positive cells and a significant increase in Tregs were observed in IDO-BMSC cocultured. Treatment of transplanted rats with IDO-BMSCs was associated with significantly prolonged graft survival. Compared with the control groups, transplanted animals treated with IDO-BMSCs had a (1) significantly higher ejection fraction and fractional shortening, (2) significantly lower expression of CD86, CD80, and MHCII, and significantly higher expression in CD274, and Tregs, and (3) significantly higher levels of interleukin-10 (IL-10), transforming growth factor beta-1 (TGF-β1), TGF-β2, and TGF-β3, and significantly lower levels of IL-2 and interferon gamma. Our results expand our understanding of the molecular mechanisms underlying suppression of heart allograft rejection via IDO-expressing BMSCs.
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