Autoimmune cholangitis in NOD.c3c4 mice is associated with cholangiocyte-specific Fas antigen deficiency

Yu Nakagome, Yoshiyuki Ueno, Takayuki Kogure, Koji Fukushima, Yuki Moritoki, William M. Ridgway, M. Eric Gershwin, Tooru Shimosegawa

研究成果: Article

22 引用 (Scopus)

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A major handicap in understanding the pathogenesis of autoimmune cholangitis has been the absence of an informative mouse model. Recently, autoimmune cholangitis, with several features similar to PBC, has been described in NOD.c3c4 mice, including anti-mitochondrial antibodies, lymphocytic portal tract infiltrates, biliary destruction and the adoptive transfer of disease to naïve recipients using liver-derived lymphocytes. A unique feature, and a characteristic quite distinct from human PBC, is the presence of bile cyst formation. We have addressed the issue of cysts in NOD.c3c4 mice by performing comprehensive microarray analysis using cholangiocytes from NOD.c3c4 mice compared to NOD controls. Several key differences in gene expression were noted in NOD.c3c4 cholangiocytes. First, there was consistent impairment in the expression of Fas antigen (CD95). Second, cholangiocytes were PCNA positive but TUNEL negative, suggesting an absence of apoptosis despite abnormal proliferation. In conclusion, we propose that autoimmune cholangitis develops in NOD.c3c4 mice secondary to impaired biliary cell apoptosis with exposure of mitochondrial antigens, loss of tolerance and subsequent development of multi-lineage anti-mitochondrial responses.

元の言語English
ページ(範囲)20-29
ページ数10
ジャーナルJournal of Autoimmunity
29
発行部数1
DOI
出版物ステータスPublished - 2007 8

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

フィンガープリント Autoimmune cholangitis in NOD.c3c4 mice is associated with cholangiocyte-specific Fas antigen deficiency' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Nakagome, Y., Ueno, Y., Kogure, T., Fukushima, K., Moritoki, Y., Ridgway, W. M., Eric Gershwin, M., & Shimosegawa, T. (2007). Autoimmune cholangitis in NOD.c3c4 mice is associated with cholangiocyte-specific Fas antigen deficiency. Journal of Autoimmunity, 29(1), 20-29. https://doi.org/10.1016/j.jaut.2007.03.004