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

Ciliang Jin, Penglei Jiang, Zhaoru Zhang, Yingli Han, Xue Wen, Lin Zheng, Wei Kuang, Jiangshan Lian, Guodong Yu, Xinyue Qian, Yue Ren, Miaomiao Lu, Lingling Xu, Weixin Chen, Jiyang Chen, Yuwei Zhou, Jinxia Xin, Ben Wang, Xi Jin (), Pengxu Qian () and Yida Yang ()
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Ciliang Jin: The First Affiliated Hospital, Zhejiang University School of Medicine
Penglei Jiang: Zhejiang University
Zhaoru Zhang: Zhejiang University
Yingli Han: Zhejiang University
Xue Wen: The First Affiliated Hospital, Zhejiang University School of Medicine
Lin Zheng: The First Affiliated Hospital, Zhejiang University School of Medicine
Wei Kuang: The First Affiliated Hospital, Zhejiang University School of Medicine
Jiangshan Lian: The First Affiliated Hospital, Zhejiang University School of Medicine
Guodong Yu: The First Affiliated Hospital, Zhejiang University School of Medicine
Xinyue Qian: Zhejiang University
Yue Ren: The First Affiliated Hospital, Zhejiang University School of Medicine
Miaomiao Lu: The First Affiliated Hospital, Zhejiang University School of Medicine
Lingling Xu: The First Affiliated Hospital, Zhejiang University School of Medicine
Weixin Chen: The First Affiliated Hospital, Zhejiang University School of Medicine
Jiyang Chen: The First Affiliated Hospital, Zhejiang University School of Medicine
Yuwei Zhou: The First Affiliated Hospital, Zhejiang University School of Medicine
Jinxia Xin: The Second Affiliated Hospital, Zhejiang University School of Medicine
Ben Wang: The Second Affiliated Hospital, Zhejiang University School of Medicine
Xi Jin: The First Affiliated Hospital, Zhejiang University School of Medicine
Pengxu Qian: Zhejiang University
Yida Yang: The First Affiliated Hospital, Zhejiang University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-53104-9

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