Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis
Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis
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DOI：
10.1007/s00595-018-1643-x
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发表时间：
2018-07-01
期刊：
影响因子：
2.5
通讯作者：
Okada, Yoshinori
中科院分区：
文献类型：
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作者：
Ishibashi, Naoya;Watanabe, Tatsuaki;Okada, Yoshinori
目的建立大鼠同种异体肺移植模型，探讨骨髓间充质干细胞（mesenchymal stromal cells，MSCs）对肺移植急性排斥反应的预防和治疗作用。移植后将MSC给予受体一次（第0天）或两次（第0天和第3天）。移植后6天，在大体和显微镜下评估急性排斥反应的分级。为阐明其相关机制，采用定量RT-PCR方法检测移植肺组织中炎性细胞因子和免疫调节受体的mRNA水平。结果术后接受MSCs的大鼠肺移植组织对急性排斥反应的保护作用明显优于未接受MSCs的对照组。结论MSC通过增强PD-L1表达和下调IL-17 A表达，调节T细胞活性，对同种异体肺移植物的急性排斥反应具有保护作用。
Purpose Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts.Methods Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR.Results The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A.Conclusion This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.