Li Lian, Luo Zhigang, Song Zhe, Zheng Liwen, Chen Tuo
Department of Urology, The Second Hospital, University of South China, Hengyang, Hunan, China.
Department of Urology, The Second Hospital, University of South China, Hengyang, Hunan, China.
Transpl Immunol. 2017 Dec;45:22-28. doi: 10.1016/j.trim.2017.08.004. Epub 2017 Aug 9.
The immunosuppressive mechanism of sinomenine in organ allotransplantation was investigated, especially its effect of blocking dendritic cell (DC) maturation, which might influence the frequency of regulatory T cells (Tregs).
Bone marrow cells from male donor Wistar rats were induced to differentiate into DCs in vitro in the presence or absence of sinomenine, and characterized by flow cytometry. These two groups of DCs were respectively injected into male recipient Sprague-Dawley rats via the tail vein, at both high and low doses. Sprague-Dawley rats receiving saline injection were used as controls. Seven days later, renal transplantation was performed from donor Wistar rats to the recipient Sprague-Dawley rats. Seven days after transplantation, spleens were collected from the recipients. The proportions of Tregs and Foxp3 Tregs to CD4 T cells were determined using flow cytometry.
With sinomenine treatment, the frequency of mature DCs was reduced, as indicated by lower expression of the surface markers CD80, CD86, and RT1B. In recipient Sprague-Dawley rats that received sinomenine-treated DCs before renal allotransplantation, the proportions of splenic Tregs and Foxp3 Tregs were significantly higher than in control recipients receiving saline or DCs without sinomenine treatment (all p<0.05). A high dose of sinomenine-treated DCs (10 cells) had a more obvious effect in increasing Tregs than the low dose (10 cells) (p<0.05).
Pre-transplant infusion of donor-derived sinomenine-induced maturation arrested DCs could result in the increase of Foxp3 Tregs in the spleens of recipients after renal allotransplantation.
研究青藤碱在器官异体移植中的免疫抑制机制，尤其是其阻断树突状细胞（DC）成熟的作用，这可能会影响调节性T细胞（Tregs）的频率。
在有或无青藤碱存在的情况下，体外诱导雄性供体Wistar大鼠的骨髓细胞分化为DC，并通过流式细胞术进行表征。将这两组DC分别以高剂量和低剂量经尾静脉注射到雄性受体Sprague-Dawley大鼠体内。接受生理盐水注射的Sprague-Dawley大鼠用作对照。7天后，将供体Wistar大鼠的肾脏移植到受体Sprague-Dawley大鼠体内。移植后7天，从受体中收集脾脏。使用流式细胞术测定Tregs和Foxp3 Tregs在CD4 T细胞中的比例。
经青藤碱处理后，成熟DC的频率降低，这表现为表面标志物CD80、CD86和RT1B的表达较低。在肾异体移植前接受青藤碱处理的DC的受体Sprague-Dawley大鼠中，脾脏Tregs和Foxp3 Tregs的比例显著高于接受生理盐水或未经青藤碱处理的DC的对照受体（所有p<0.05）。高剂量（10个细胞）的青藤碱处理的DC在增加Tregs方面比低剂量（10个细胞）有更明显的效果（p<0.05）。
移植前输注供体来源的青藤碱诱导成熟停滞的DC可导致肾异体移植后受体脾脏中Foxp3 Tregs增加。
