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Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression

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机构: [1]Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China. [2]Inspection Department of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, China. [3]Kunming Medical University, Kunming, China.
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关键词: Liver cirrhosis CD8-positive T-lymphocytes Single-cell RNA sequencing Chemokine CXCL13

摘要:
: Liver cirrhosis involves chronic inflammation and progressive fibrosis. Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear.: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis.: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer.: In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

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大类 | 3 区 医学
小类 | 3 区 胃肠肝病学
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第一作者机构: [1]Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China.
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