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Premium Natural killer T cells exacerbate liver injury in a transforming growth factor β receptor II dominant‐negative mouse model of primary biliary cirrhosis
Chuang YaHui,
Lian ZheXiong,
Yang GuoXiang,
Shu ShangAn,
Moritoki Yuki,
Ridgway William M.,
Ansari Aftab A.,
Kronenberg Mitchell,
Flavell Richard A.,
Gao Bin,
Gershwin M. Eric
Publication year2008
Publication title
Resource typeJournals
PublisherWiley Subscription Services
Abstract Primary biliary cirrhosis (PBC) is an organ‐specific autoimmune liver disease characterized by the presence of antimitochondrial antibodies and the destruction of small intrahepatic bile ducts with portal inflammation. In previous studies, we reported that both CD1d expression and the frequency of CD1d‐restricted natural killer T (NKT) cells were increased in the livers of patients with PBC. To define a specific role of CD1d‐restricted NKT cells in the pathogenesis of PBC, particularly early events, we investigated the function of hepatic CD1d‐restricted NKT cells in our transforming growth factor β (TGF‐β) receptor II dominant‐negative (dnTGFβRII) mouse model of PBC. We generated CD1d −/− and CD1d +/− dnTGFβRII mice and performed a comparative study of liver immunopathology. We report herein that these dnTGFβRII mice demonstrate a massive increase of hyperactive CD1d‐restricted NKT cells within the hepatic tissues. CD1d −/− dnTGFβRII mice, which lack CD1d‐restricted CD1d‐restricted NKT cells, exhibit significantly decreased hepatic lymphoid cell infiltrates and milder cholangitis compared with CD1d +/− dnTGFβRII mice. Interestingly, there was a significant increase in the production of interferon‐γ in hepatic CD1d‐restricted NKT cells activated by α‐galactosylceramide in young but not older dnTGFβRII mice, suggesting an age‐dependent role of CD1d‐restricted NKT cells. Conclusion: These data demonstrate that CD1d‐restricted NKT cells in dnTGFβRII mice are a critical factor in liver injury. (H EPATOLOGY 2008.)
Subject(s)biology , cd1d , hepatology , immune system , immunology , medicine , natural killer t cell , primary biliary cirrhosis , t cell
SCImago Journal Rank5.488

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