title: Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells.
abstract: Primary biliary cirrhosis (PBC) is characterized by the highly selective autoimmune injury of small intrahepatic bile ducts, despite widespread distribution of mitochondrial autoantigens. On this basis, it has been suggested that the targeted biliary epithelial cells (BECs) play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. To address this issue, we challenged BECs from patients with PBC and controls using multiple Toll-like receptor (TLR) ligands as well as autologous liver-infiltrating mononuclear cells (LMNCs) with subsequent measurement of BEC phenotype and chemokine production and LMNC chemotaxis by quantifying specific chemokines. Our data reflect that BECs from PBC patients and controls express similar levels of TLR subtypes, CD40, and human leukocyte antigen DRalpha (HLA-DRalpha) and produce equivalent amounts of chemokines in our experimental conditions. Interestingly, however, BEC-expressed chemokines elicit enhanced transmigration of PBC LMNCs compared with controls. Furthermore, the addition of autologous LMNCs to PBC BECs led to the production of higher levels of chemokines and enhanced the expression of CD40 and HLA-DRalpha.
  
  
  CONCLUSIONS
  We submit that the proinflammatory activity of BECs in PBC is secondary to the intervention of LMNCs and is not determined per se. These data support the hypothesis that BECs are in fact "innocent victims" of autoimmune injury and that the adaptive immune response is critical in PBC.
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. sshimoda@intmed1.med.kyushu-u.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimoda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Niiro
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yoshizumi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Soejima
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Komori
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Carlo
authors.initials: C
authors.lastname: Selmi
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000276:immunology* / Q000473:pathology; D019013:CD40 Antigens / Q000032:analysis; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology; D008297:Male; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D018925:Chemokines; D006684:HLA-DR Antigens; D051193:Toll-Like Receptors