Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis Article Swipe

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Xi Li , Yan Li , Jintao Xiao , Huiwen Wang , Yan Guo , Xiuru Mao , Pan Shi , Yanliang Hou , Xiaoxun Zhang , Nan Zhao , Ming‐Hua Zheng , Yonghong He , Jingjing Ding , Ya Tan , Min Liao , Ling Li , Ying Peng , Xuan Li , Qiong Pan , Qiaoling Xie , Qiao Li , Jianwei Li , Ying Li , Zhe Chen , Yongxiu Huang , David N. Assis , Shi‐Ying Cai , James L. Boyer , Huang Xue-quan , Can‐E Tang , Xiaowei Liu , Shifang Peng , Jin Chai ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1038/s41467-022-34606-w

Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease. Using single-cell RNA sequencing (scRNA-seq), fluorescence-activated-cell-sorting, multiplex immunofluorescence (IF) and RNAscope analyses, we identified unique DUOX2 + ACE2 + small cholangiocytes in human and mouse livers. Their selective decrease in PBC patients was associated with the severity of disease. Moreover, proteomics, scRNA-seq, and qPCR analyses indicated that polymeric immunoglobulin receptor (pIgR) was highly expressed in DUOX2 + ACE2 + cholangiocytes. Serum anti-pIgR autoantibody levels were significantly increased in PBC patients, regardless of positive and negative AMA-M2. Spatial transcriptomics and multiplex IF revealed that CD27 + memory B and plasma cells accumulated in the hepatic portal tracts of PBC patients. Collectively, DUOX2 + ACE2 + small cholangiocytes are pathogenic targets in PBC, and preservation of DUOX2 + ACE2 + cholangiocytes and targeting anti-pIgR autoantibodies may be valuable strategies for therapeutic interventions in PBC.

Related Topics

Primary Sclerosing Cholangitis

Concepts

Primary sclerosing cholangitis Primary (astronomy) Bile Duct Diseases Cholestasis Medicine Biology Gastroenterology Internal medicine Chemistry Physics Disease Bile duct Astronomy

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Type: article
Language: en
Landing Page: https://doi.org/10.1038/s41467-022-34606-w
PDF: https://www.nature.com/articles/s41467-022-34606-w.pdf
OA Status: gold
Cited By: 51
References: 37
Related Works: 10
OpenAlex ID: https://openalex.org/W4319827711

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OpenAlex ID: https://openalex.org/W4319827711

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DOI: https://doi.org/10.1038/s41467-022-34606-w

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Title: Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis

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Type: article

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Language: en

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Publication year: 2023

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Publication date: 2023-02-09

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Authors: Xi Li, Yan Li, Jintao Xiao, Huiwen Wang, Yan Guo, Xiuru Mao, Pan Shi, Yanliang Hou, Xiaoxun Zhang, Nan Zhao, Ming‐Hua Zheng, Yonghong He, Jingjing Ding, Ya Tan, Min Liao, Ling Li, Ying Peng, Xuan Li, Qiong Pan, Qiaoling Xie, Qiao Li, Jianwei Li, Ying Li, Zhe Chen, Yongxiu Huang, David N. Assis, Shi‐Ying Cai, James L. Boyer, Huang Xue-quan, Can‐E Tang, Xiaowei Liu, Shifang Peng, Jin Chai

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Landing page: https://doi.org/10.1038/s41467-022-34606-w

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PDF URL: https://www.nature.com/articles/s41467-022-34606-w.pdf

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Concepts: Primary sclerosing cholangitis, Primary (astronomy), Bile Duct Diseases, Cholestasis, Medicine, Biology, Gastroenterology, Internal medicine, Chemistry, Physics, Disease, Bile duct, Astronomy

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Cited by: 51

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Citations by year (recent): 2025: 22, 2024: 20, 2023: 9

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