Journal Article

Single-cell RNA sequencing reveals the pro-inflammatory roles of liver-resident Th1-like cells in primary biliary cholangitis

Xu, Lingling, Chen, Jiyang, Jin, Xi, Zhou, Yuwei, Wang, Ben, Han, Yingli, Zheng, Lin, Zhang, Zhaoru, Xin, Jinxia, Lian, Jiangshan, Wen, Xue, Yang, Yida, Qian, Xinyue, Jin, Ciliang, Qian, Pengxu, Ren, Yue, Jiang, Penglei, Yu, Guodong, Chen, Weixin, Kuang, Wei, Lu, Miaomiao

2024

Overview

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by multilineage immune dysregulation, which subsequently causes inflammation, fibrosis, and even cirrhosis of liver. Due to the limitation of traditional assays, the local hepatic immunopathogenesis of PBC has not been fully characterized. Here, we utilize single-cell RNA sequencing technology to depict the immune cell landscape and decipher the molecular mechanisms of PBC patients. We reveal that cholangiocytes and hepatic stellate cells are involved in liver inflammation and fibrosis. Moreover, Kupffer cells show increased levels of inflammatory factors and decreased scavenger function related genes, while T cells exhibit enhanced levels of inflammatory factors and reduced cytotoxicity related genes. Interestingly, we identify a liver-resident Th1-like population with JAK-STAT activation in the livers of both PBC patients and murine PBC model. Finally, blocking the JAK-STAT pathway alleviates the liver inflammation and eliminates the liver-resident Th1-like cells in the murine PBC model. In conclusion, our comprehensive single-cell transcriptome profiling expands the understanding of pathological mechanisms of PBC and provides potential targets for the treatment of PBC in patients. Primary biliary cholangitis is a chronic autoimmune disease critically linked to immunological dysregulation but the local immune-pathogenesis is poorly understood. Here the authors present single cell transcriptomic characterisation of primary biliary cholangitis and implicates Th1 like cells in a murine model.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45/91 / 49/31 / 631/250/38 / 631/553/1833 / 64/60 / 692/420/256/2515 / 692/699/1503/1328/1325/1606 / 96/21 / Animal models / Animals / Autoimmune diseases / Cholangitis / Cirrhosis / Cytotoxicity / Disease Models, Animal / Female / Fibrosis / Gene Expression Profiling / Gene sequencing / Genes / Hepatic Stellate Cells - immunology / Hepatic Stellate Cells - metabolism / Hepatic Stellate Cells - pathology / Hepatocytes / Humanities and Social Sciences / Humans / Immune system / Immunology / Immunopathogenesis / Inflammation / Inflammation - genetics / Inflammation - metabolism / Inflammation - pathology / Janus Kinases - genetics / Janus Kinases - metabolism / Kupffer cells / Kupffer Cells - immunology / Kupffer Cells - metabolism / Liver / Liver - immunology / Liver - metabolism / Liver - pathology / Liver Cirrhosis, Biliary - genetics / Liver Cirrhosis, Biliary - immunology / Liver Cirrhosis, Biliary - metabolism / Liver Cirrhosis, Biliary - pathology / Liver diseases / Lymphocytes / Lymphocytes T / Male / Mice / Mice, Inbred C57BL / Molecular modelling / multidisciplinary / Pathogenesis / Ribonucleic acid / RNA / Science / Science (multidisciplinary) / Sequence Analysis, RNA - methods / Signal Transduction / Single-Cell Analysis - methods / STAT Transcription Factors - genetics / STAT Transcription Factors - metabolism / Stellate cells / Th1 Cells - immunology / Transcriptome / Transcriptomes / Transcriptomics