A Mouse Model of Autoimmune Cholangitis via Syngeneic Bile Duct Protein Immunization

Research output: Contribution to journalArticlepeer-review


  • Wen-Tao Ma
  • Qing-Zhi Liu
  • Jing-Bo Yang
  • Yan-Qing Yang
  • Zhi-Bin Zhao
  • Hong-Di Ma
  • M Eric Gershwin
  • Zhe-Xiong Lian

Colleges, School and Institutes

External organisations

  • College of Veterinary Medicine, Northwest Agriculture and Forestry University, Yangling, 712100, China.
  • Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
  • Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA.
  • Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, 230027, China. zxlian1@ustc.edu.cn.


Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the destruction of interlobular biliary ductules, which progressively leads to cholestasis, hepatic fibrosis, cirrhosis, and eventually liver failure. Several mouse models have been used to clarify the pathogenesis of PBC and are generally considered reflective of an autoimmune cholangitis. Most models focus on issues of molecular mimicry between the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC and xenobiotic cross reactive chemicals. None have focused on the classic models of breaking tolerance, namely immunization with self-tissue. Here, we report a novel mouse model of autoimmune cholangitis via immunization with syngeneic bile duct protein (BDP). Our results demonstrate that syngeneic bile duct antigens efficiently break immune tolerance of recipient mice, capturing several key features of PBC, including liver-specific inflammation focused on portal tract areas, increased number and activation state of CD4 and CD8 T cells in the liver and spleen. Furthermore, the germinal center (GC) responses in the spleen were more enhanced in our mouse model. Finally, these mice were 100% positive for anti-mitochondrial antibodies (AMAs). In conclusion, we developed a novel mouse model of PBC that may help to elucidate the detailed mechanism of this complex disease.


Original languageEnglish
Article number15246
JournalScientific Reports
Issue number1
Publication statusPublished - 10 Nov 2017


  • Autoimmunity, Mechanisms of disease