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

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 b...

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Published ineLife Vol. 13
Main Authors Jin, Yong, Xing, Jiayu, Dai, Chenyu, Jin, Lei, Zhang, Wanying, Tao, Qianqian, Hou, Mei, Li, Ziyi, Yang, Wen, Feng, Qiyu, Wang, Hongyang, Yu, Qingsheng
Format Journal Article
LanguageEnglish
Published England eLife Science Publications, Ltd 30.12.2024
eLife Sciences Publications, Ltd
eLife Sciences Publications Ltd
Subjects
Adult
Analysis
B cells
Cholecystitis
Cholecystitis - diagnosis
Cholecystitis - genetics
Cholecystitis - immunology
Fatigue
Female
Hepatolenticular Degeneration - complications
Hepatolenticular Degeneration - genetics
Hepatolenticular Degeneration - immunology
Hepatolenticular Degeneration - pathology
Humans
immune cell dysfunction
Immune System Exhaustion
Immunology and Inflammation
Killer cells
Killer Cells, Natural - immunology
Liver
Liver - immunology
Liver - pathology
Liver diseases
Male
Medical research
Medicine
Medicine, Experimental
metabolic abnormalities
Middle Aged
NK cell exhaustion
Physiological aspects
Prognosis
Retrospective Studies
RNA
RNA sequencing
Sequence Analysis, RNA
Single-Cell Analysis
United States
Massachusetts
China
inflammation
metabolic abnormalities
immune cell dysfunction
medicine
NK cell exhaustion
human
immunology
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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.
AbstractList 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.
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.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.
Audience Academic
Author Jin, Yong
Yang, Wen
Hou, Mei
Wang, Hongyang
Zhang, Wanying
Feng, Qiyu
Dai, Chenyu
Li, Ziyi
Jin, Lei
Tao, Qianqian
Yu, Qingsheng
Xing, Jiayu
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Keywords inflammation
metabolic abnormalities
immune cell dysfunction
medicine
NK cell exhaustion
human
immunology
Language English
License 2024, Jin, Xing, Dai et al.
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  article-title: Conservative treatment of acute cholecystitis: a systematic review and pooled analysis
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  article-title: Prevalent pathogenic variants of ATP7B in chinese patients with wilson’s disease: geographical distribution and founder effect
  publication-title: Genes
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Snippet Metabolic abnormalities associated with liver disease have a significant impact on the risk and prognosis of cholecystitis. However, the underlying mechanism...
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SubjectTerms Adult
Analysis
B cells
Cholecystitis
Cholecystitis - diagnosis
Cholecystitis - genetics
Cholecystitis - immunology
Fatigue
Female
Hepatolenticular Degeneration - complications
Hepatolenticular Degeneration - genetics
Hepatolenticular Degeneration - immunology
Hepatolenticular Degeneration - pathology
Humans
immune cell dysfunction
Immune System Exhaustion
Immunology and Inflammation
Killer cells
Killer Cells, Natural - immunology
Liver
Liver - immunology
Liver - pathology
Liver diseases
Male
Medical research
Medicine
Medicine, Experimental
metabolic abnormalities
Middle Aged
NK cell exhaustion
Physiological aspects
Prognosis
Retrospective Studies
RNA
RNA sequencing
Sequence Analysis, RNA
Single-Cell Analysis
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Title NK cell exhaustion in Wilson’s disease revealed by single-cell RNA sequencing predicts the prognosis of cholecystitis
URI https://www.ncbi.nlm.nih.gov/pubmed/39854622
https://www.proquest.com/docview/3159693791
https://pubmed.ncbi.nlm.nih.gov/PMC11684787
https://doaj.org/article/383f60c9c6d746c1a13c02b085756ea8
Volume 13
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