Mesenchymal stem cells ameliorate experimental autoimmune hepatitis by activation of the programmed death 1 pathway
Mesenchymal stem cells ameliorate experimental autoimmune hepatitis by activation of the programmed death 1 pathway
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DOI：
10.1016/j.imlet.2014.10.021
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发表时间：
2014-12-01
影响因子：
4.4
通讯作者：
Chen, Yong-Ping
中科院分区：
文献类型：
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作者：
Chen, Yi;Chen, Si;Chen, Yong-Ping
以往的研究表明，骨髓间充质干细胞（MSCs）移植在许多自身免疫性疾病的有益效果。然而，很少有研究集中在骨髓间充质干细胞对自身免疫性肝炎的影响。本研究旨在观察骨髓间充质干细胞（bone mesenchymal stem cells，BMSCs）移植对小鼠实验性自身免疫性肝炎（experimental autoimmune hepatitis，EAH）的治疗作用，并探讨其可能的作用机制。将骨髓间充质干细胞静脉注射到EAH小鼠中。检测各组大鼠血清ALT、AST水平及肝组织病理学改变，评价肝功能及炎症程度。采用酶联免疫吸附试验（ELISA）、逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blotting）检测程序性死亡配体1、IL-17和IL-23的表达。经血清生化指标和病理学检查，BMSCs处理的小鼠尤其是多次给药的小鼠表现出显著的肝损伤减轻。与模型组相比，BMSCs干预后IL-17表达下调，PD-L1和IL-23表达上调。综上所述，本研究结果表明，BMSCs移植，特别是多次给药，可能通过抑制IL-17和上调PD-L1发挥免疫抑制作用，改善EAH。(C)2014爱思唯尔有限公司版权所有。
Previous studies have shown beneficial effects of mesenchymal stem cells (MSCs) transplantation in many autoimmune diseases. However, few studies have focused on the effects of MSCs on autoimmune hepatitis. In our study, we investigated the therapeutic effects of BMSCs (bone mesenchymal stem cells) transplantation in mouse experimental autoimmune hepatitis (EAH) and explored the potential mechanism. BMSCs were injected intravenously into EAH mice. Then, serum levels of ALT and AST, and pathologic alteration of liver tissue were measured to evaluate the liver function and inflammation degree. The expressions of programmed death ligand 1, IL-17 and IL-23 were detected by enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and western blotting. Upon serum biochemical levels and pathological examination, the BMSCs-treated mice especially with multiple dosing administration showed significantly reduction of liver damage. Moreover, the expression of IL-17 was down-regulated by BMSCs intervention as compared to the model group, whereas the PD-L1 and IL-23 were up-regulated following the administration of MSCs. In conclusion, the results of this study suggest that BMSCs transplantation, especially on multiple dosing, may exert immunosuppression effect to ameliorate EAH through the inhibition of IL-17 and up-regulation of PD-L1. (C) 2014 Elsevier B.V. All rights reserved.