Dynamic immune cell profiling identified natural killer cell shift as the key event in early allograft dysfunction after liver transplantation
Dynamic immune cell profiling identified natural killer cell shift as the key event in early allograft dysfunction after liver transplantation
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动态免疫细胞图谱证实自然杀伤细胞转移是肝移植术后早期移植功能障碍的关键事件
DOI：
10.1111/cpr.13568
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发表时间：
2023-10
影响因子：
8.5
通讯作者：
D. Lu;Xinyu Yang;Linhui Pan;Zhengxing Lian;W. Tan;Jianyong Zhuo;Modan Yang;Zuyuan Lin;Q. Wei;Jun Chen;Shusen Zheng;Xiao Xu
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文献类型：
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作者：
D. Lu;Xinyu Yang;Linhui Pan;Zhengxing Lian;W. Tan;Jianyong Zhuo;Modan Yang;Zuyuan Lin;Q. Wei;Jun Chen;Shusen Zheng;Xiao Xu
早期同种异体移植功能障碍(EAD)是肝移植后一种危及生命且发展迅速的并发症。其潜在的机制需要更好地了解，目前还没有一个有效的治疗靶点。本研究回顾分析了109例肝移植患者的外周免疫细胞CD3/4/8/16/19/45/56的动态变化(移植前和移植后2-4天)。总体而言，109名患者中有35人在肝移植后发生了EAD。我们观察到自然杀伤细胞比例显著下降(NK细胞移位，p=0.008)。NK细胞移位与冷缺血时间呈线性相关(p=0.016)，并可能与受体的预后有关。在小鼠模型中，缺血/再灌注(I/R)治疗诱导NK细胞从外周血重新聚集到肝组织。在I/R和肝移植模型中，NK细胞去除阻断了包括CD8+CD127+T细胞在内的一系列免疫级联反应，有效地抑制了肝细胞损伤。我们进一步发现，I/R处理增加了肝脏中自然杀伤分子2成员D(NKG2D)的配体的表达，NKG2D是NK细胞中主要的激活细胞表面受体。阻断NKG2D对I/R损伤有相似的保护作用，提示其在NK细胞活化及随后的免疫损伤中发挥作用。我们的发现为从先天免疫反应到床边EAD的转换搭建了一座桥梁。外周血NK细胞移位与肝移植后EAD的发生有关。NKG2D介导的NK细胞活化是一种潜在的治疗靶点。
Early allograft dysfunction (EAD) is a life‐threatening and fast‐developing complication after liver transplantation. The underlying mechanism needs to be better understood, and there has yet to be an efficient therapeutic target. This study retrospectively reviewed 109 patients undergoing liver transplantation, with dynamic profiling of CD3/4/8/16/19/45/56 on the peripheral immune cells (before transplant and 2–4 days after). Altogether, 35 out of the 109 patients developed EAD after liver transplantation. We observed a significant decrease in the natural killer cell proportion (NK cell shift, p = 0.008). The NK cell shift was linearly correlated with cold ischemic time (p = 0.016) and was potentially related to the recipients' outcomes. In mouse models, ischemic/reperfusion (I/R) treatments induced the recruitment of NK cells from peripheral blood into liver tissues. NK cell depletion blocked a series of immune cascades (including CD8+ CD127+ T cells) and inhibited hepatocyte injury effectively in I/R and liver transplantation models. We further found that I/R treatment increased hepatic expression of the ligands for natural killer group 2 member D (NKG2D), a primary activating cell surface receptor in NK cells. Blockade of NKG2D showed a similar protective effect against I/R injury, indicating its role in NK cell activation and the subsequent immunological injury. Our findings built a bridge for the translation from innate immune response to EAD at the bedside. Peripheral NK cell shift is associated with the incidence of EAD after liver transplantation. NKG2D‐mediated NK cell activation is a potential therapeutic target.