High Mobility Group Box 1 Contributes to the Acute Rejection of Liver Allografts by Activating Dendritic Cells.
High Mobility Group Box 1 Contributes to the Acute Rejection of Liver Allografts by Activating Dendritic Cells.
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DOI：
10.3389/fimmu.2021.679398
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发表时间：
2021
影响因子：
7.3
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Chen Y;Zhang W;Bao H;He W;Chen L
受者T细胞识别供体同种异体抗原引起的急性排斥反应导致肝移植受者的移植物衰竭。高迁移率族蛋白1（HMGB 1）是一种炎症介质，在肝移植急性排斥反应中的作用尚不清楚。本研究成功建立大鼠原位肝移植模型，分析HMGB 1在肝移植中的表达模式及其在促进树突状细胞（DCs）成熟、促进T细胞增殖和分化中的作用。移植后5天和10天，同种异体移植物显示HMGB 1表达显著上调，伴有血清转氨酶水平升高和CD 3+和CD 86+炎性细胞浸润。体外实验显示HMGB 1可增加骨髓来源DC表面共刺激分子（CD 80、CD 83和MHC II类分子）的表达。HMGB 1致敏的DC诱导幼稚CD 4 + T细胞分化为Th 1和Th 17亚群，分别分泌IFN-γ和IL-17。进一步的体内实验证实，在供体肝脏保存期间给予天然HMGB 1抑制剂-这些结果提示HMBG 1参与了肝移植急性排斥反应的发生，并可能成为避免肝移植急性排斥反应的一个候选治疗靶点。
Acute rejection induced by the recognition of donor alloantigens by recipient T cells leads to graft failure in liver transplant recipients. The role of high mobility group box 1 (HMGB1), an inflammatory mediator, in the acute allograft rejection of liver transplants is unknown. Here, rat orthotopic liver transplantation was successfully established to analyze the expression pattern of HMGB1 in liver allografts and its potential role in promoting the maturation of dendritic cells (DCs) to promote T cell proliferation and differentiation. Five and 10 days after transplantation, allografts showed a marked upregulation of HMGB1 expression accompanied by elevated levels of serum transaminase and CD3+ and CD86+ inflammatory cell infiltration. Furthermore, in vitro experiments showed HMGB1 increased the expressions of co-stimulatory molecules (CD80, CD83, and MHC class II) on bone marrow-derived DCs. HMGB1-pulsed DCs induced naive CD4+ T cells to differentiate to Th1 and Th17 subsets secreting IFN-γ and IL-17, respectively. Further in vivo experiments confirmed the administration of glycyrrhizic acid, a natural HMGB1 inhibitor, during donor liver preservation had therapeutic effects by reducing inflammation and hepatocyte damage reflected by a decline in serum transaminase and prolonged allograft survival time. These results suggest the involvement of HMBG1 in acute liver allograft rejection and that it might be a candidate therapeutic target to avoid acute rejection after liver transplantation.
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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