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单细胞RNA测序揭示的威尔逊病中自然杀伤细胞耗竭可预测胆囊炎的预后。

NK cell exhaustion in Wilson's disease revealed by single-cell RNA sequencing predicts the prognosis of cholecystitis.

作者信息

Jin Yong, Xing Jiayu, Dai Chenyu, Jin Lei, Zhang Wanying, Tao Qianqian, Hou Mei, Li Ziyi, Yang Wen, Feng Qiyu, Wang Hongyang, Yu Qingsheng

机构信息

Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Department of Cadre Cardiology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.

出版信息

Elife. 2024 Dec 30;13:RP98867. doi: 10.7554/eLife.98867.

DOI:10.7554/eLife.98867
PMID:39854622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11684787/
Abstract

Metabolic abnormalities associated with liver disease have a significant impact on the risk and prognosis of cholecystitis. However, the underlying mechanism remains to be elucidated. Here, we investigated this issue using Wilson's disease (WD) as a model, which is a genetic disorder characterized by impaired mitochondrial function and copper metabolism. Our retrospective clinical study found that WD patients have a significantly higher incidence of cholecystitis and a poorer prognosis. The hepatic immune cell landscape using single-cell RNA sequencing showed that the tissue immune microenvironment is altered in WD, mainly a major change in the constitution and function of the innate immune system. Exhaustion of natural killer (NK) cells is the fundamental factor, supported by the upregulated expression of inhibitory receptors and the downregulated expression of cytotoxic molecules, which was verified in clinical samples. Further bioinformatic analysis confirmed a positive correlation between NK cell exhaustion and poor prognosis in cholecystitis and other inflammatory diseases. The study demonstrated dysfunction of liver immune cells triggered by specific metabolic abnormalities in WD, with a focus on the correlation between NK cell exhaustion and poor healing of cholecystitis, providing new insights into the improvement of inflammatory diseases by assessing immune cell function.

摘要

与肝脏疾病相关的代谢异常对胆囊炎的风险和预后有重大影响。然而，其潜在机制仍有待阐明。在此，我们以威尔逊病（WD）为模型对这一问题进行了研究，WD是一种以线粒体功能和铜代谢受损为特征的遗传性疾病。我们的回顾性临床研究发现，WD患者胆囊炎的发病率显著更高，预后更差。利用单细胞RNA测序分析肝脏免疫细胞图谱显示，WD患者的组织免疫微环境发生了改变，主要是固有免疫系统的组成和功能发生了重大变化。自然杀伤（NK）细胞耗竭是根本因素，这在临床样本中得到了验证，表现为抑制性受体表达上调和细胞毒性分子表达下调。进一步的生物信息学分析证实，NK细胞耗竭与胆囊炎及其他炎症性疾病的不良预后呈正相关。该研究证明了WD中特定代谢异常引发的肝脏免疫细胞功能障碍，重点关注NK细胞耗竭与胆囊炎愈合不良之间的相关性，为通过评估免疫细胞功能改善炎症性疾病提供了新的见解。

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