ORIGINAL ARTICLES

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

Motoko Sasaki, Hiroko Ikeda, Seiko Sawada, Yasunori Sato and Yasuni Nakanuma

Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

Correspondence to:
Dr Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan; pbcpsc{at}kenroku.kanazawa-u.ac.jp

Background: 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⁺CD25^high regulatory T cells (Tregs) expressing Forkhead box P3 (Foxp3) play an active role in immunological self-tolerance.

Aims: To investigate whether Foxp3+Tregs are involved in the pathogenesis of PBC.

Methods: Foxp3+Tregs was detected immunohistochemically in livers from patients with PBC (n = 27), chronic viral hepatitis (CVH) (n = 15), and normal subjects (n = 10). The distribution of Tregs in portal tracts was semi-quantitatively evaluated in each groups. Levels of Foxp3, IL-10, TGFβ, IFN and TNF mRNA was evaluated in PBC (n = 15) and control livers (n = 21) using semi-quantitative reverse transcriptase-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 disease. 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). IFN and TNF mRNA was high in early PBC and CVH livers.

Conclusion: Results of this evaluation of Foxp3+Tregs do not suggest that the reduced regulatory function accounts for the development of CNSDC in PBC.

Abbreviations: CNSDC, chronic non-suppurative destructive cholangitis; CVH, chronic viral hepatitis; Foxp3, Forkhead box P3; IL, interleukin; IFN, interferon; PBC, primary biliary cirrhosis; RT, reverse transcriptase; TGF, transforming growth factor; Th, T helper; TNF, tumour necrosis factor; Tregs, regulatory T cells

Keywords: primary biliary cirrhosis; regulatory T cells; Foxp3; IL-10; TGFβ; autoimmunity

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