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Naturally-occurring regulatory T cells are increased in inflamed portal tracts with cholangiopathy in primary biliary cirrhosis
  1. Motoko Sasaki (m8sasaki{at}
  1. Kanazawa University Graduate School of Medicine, Japan
    1. Hiroko Ikeda
    1. Kanazawa University Graduate School of Medicine, Japan
      1. Seiko Sawada
      1. Kanazawa University Graduate School of Medicine, Japan
        1. Yasunori Sato
        1. Kanazawa University Graduate School of Medicine, Japan
          1. Yasuni Nakanuma (pbcpsc{at}
          1. Kanazawa University School of Medicine, Japan


            Aims: Primary biliary cirrhosis (PBC) is an autoimmune liver disease targeting the intrahepatic small bile ducts showing chronic non-suppurative destructive cholangitis (CNSDC). Recent studies suggest that naturally-occurring CD4+CD25high regulatory T cells (Tregs) expressing Forkhead box P3 (Foxp3) play an active role in immunological self-tolerance. In this study, we investigated whether Foxp3+Tregs are involved in the pathogenesis of PBC or not. Methods: Foxp3+Tregs was detected immunohistochemically in livers from the patients with PBC (n=27), chronic viral hepatitis (CVH) (n=15), and normal livers (n=10). The distribution of Tregs in portal tracts was semi-quantitatively evaluated in each groups. The level of Foxp3, IL-10, TGFβ, IFNγ and TNFα mRNA was evaluated in PBC (n=15) and control livers (n=21) using semi-quantitative RT-PCR.

            Results: In PBC and CVH livers, the amounts of infiltrating Foxp3+Tregs in portal tracts were in parallel with the degree of portal inflammation irrespective of diseases. The infiltration of Foxp3+Tregs into portal tracts with CNSDC in PBC was foremost in comparison with inflamed portal tracts in CVH or those without CNSDC in PBC (p<0.05). Focally, Tregs infiltrated into the biliary epithelial layer at the site of CNSDC. The level of Foxp3, IL-10 and TGFβ mRNA expression was high in PBC compared with normal livers (p<0.05). IFNγ and TNFα mRNA was high in early PBC and CVH livers.

            Conclusion The evaluation of Foxp3+Tregs did not support that the reduced regulatory function account for the development of CNSDC in PBC.

            • Foxp3
            • IL-10
            • TGF-beta
            • primary biliary cirrhosis
            • regulartory T cells

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