Naturally-occurring regulatory T cells are increased in inflamed portal tracts with cholangiopathy in primary biliary cirrhosis

Abstract

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.