Single-cell RNA sequencing reveals the pro-inflammatory roles of liver-resident Th1-like cells in primary biliary cholangitis
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.
Authors
- Pengxu Qian (ORCID: https://orcid.org/0000-0001-5636-6704)
- Yingli Han (ORCID: https://orcid.org/0000-0003-3421-0965)
- W H Chen
- Lin Ping Zheng (ORCID: https://orcid.org/0000-0001-5617-5895)
- Penglei Jiang (ORCID: https://orcid.org/0000-0002-5518-7437)
- Jiyang Chen (ORCID: https://orcid.org/0000-0003-0043-0193)
- Xinyue Qian (ORCID: https://orcid.org/0009-0009-1788-2525)
- Yuwei Zhou (ORCID: https://orcid.org/0000-0002-6110-9013)
- Yida Yang (ORCID: https://orcid.org/0000-0002-9673-0969)
- Xue Lei Wen
- Zhaoru Zhang (ORCID: https://orcid.org/0000-0001-6125-8660)
- Ben Wang (ORCID: https://orcid.org/0000-0002-4134-1835)
- Lingling Xu (ORCID: https://orcid.org/0000-0002-0142-0053)
- Xi Jin (ORCID: https://orcid.org/0000-0002-2975-977X)
- Jiangshan Lian (ORCID: https://orcid.org/0000-0003-4419-2027)
- Guodong Yu (ORCID: https://orcid.org/0000-0003-1139-9021)
- Miaomiao Lu
- Yue Ren
- Wei Kuang
- Ciliang Jin
- Jinxia Xin
Institutions
- Wenzhou Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- National Clinical Research Center for Digestive Diseases (CN)
- National Center for Infectious Diseases (US)
- First Affiliated Hospital Zhejiang University (CN)
- State Key Laboratory of Diagnosis and Treatment of Infectious Diseases
- Zhejiang University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-07
- DOI
- https://doi.org/10.1038/s41467-024-53104-9
- Citations
- 35
- Primary Topic
- Liver Diseases and Immunity
- Type
- article
- Field-Weighted Citation Impact
- 12.93
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Zhejiang Province