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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 (US)
Article number15246
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Cholangitis
Bile Ducts
Immunization
Proteins
Spleen
Dihydrolipoyllysine-Residue Acetyltransferase
Molecular Mimicry
Immune Tolerance
Germinal Center
Liver
Cholestasis
Liver Failure
Autoantigens
Xenobiotics
Liver Cirrhosis
Autoimmune Diseases
Liver Diseases
Anti-Idiotypic Antibodies
Fibrosis
Inflammation

ASJC Scopus subject areas

  • General

Cite this

Ma, W. T., Liu, Q. Z., Yang, J. B., Yang, Y. Q., Zhao, Z. B., Ma, H. D., ... Lian, Z. X. (2017). A Mouse Model of Autoimmune Cholangitis via Syngeneic Bile Duct Protein Immunization. Scientific Reports, 7(1), [15246]. https://doi.org/10.1038/s41598-017-15661-6

A Mouse Model of Autoimmune Cholangitis via Syngeneic Bile Duct Protein Immunization. / Ma, Wen Tao; Liu, Qing Zhi; Yang, Jing Bo; Yang, Yan Qing; Zhao, Zhi Bin; Ma, Hong Di; Gershwin, M. Eric; Lian, Zhe Xiong.

In: Scientific Reports, Vol. 7, No. 1, 15246, 01.12.2017.

Research output: Contribution to journalArticle

Ma, Wen Tao ; Liu, Qing Zhi ; Yang, Jing Bo ; Yang, Yan Qing ; Zhao, Zhi Bin ; Ma, Hong Di ; Gershwin, M. Eric ; Lian, Zhe Xiong. / A Mouse Model of Autoimmune Cholangitis via Syngeneic Bile Duct Protein Immunization. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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