title: Significance of periductal Langerhans cells and biliary epithelial cell-derived macrophage inflammatory protein-3α in the pathogenesis of primary biliary cirrhosis.
abstract: OBJECTIVE
  To clarify the primary biliary cirrhosis (PBC)-specific antigen-presenting mechanism, we examined the distribution and phenotypic characteristics of infiltrating dendritic cells (DCs) with respect to bile ducts and the mechanism of migration in terms of the periductal cytokine milieu and biliary innate immunity.
  
  
  RESULTS
  Immunohistochemistry using liver sections from patients with PBC and controls revealed that blood dendritic cell antigen (BDCA)-2(+) plasmacytoid DCs were found mainly in the portal tracts in PBC and the controls, but their distribution was not related to bile ducts. BDCA-1(+) and CD19(-) myeloid DCs were also found in portal tracts in PBC and the controls and, in particular, Langerin+Langerhans cells (LCs) were dominantly scattered around or within biliary epithelial layers of the damaged bile ducts in PBC. Moreover, experiments with cultured human biliary epithelial cells (BECs) showed that an LC-attracting chemokine, macrophage inflammatory protein-3α, was produced by BECs in the response to cytokines [interleukin (IL)-1β, tumour necrosis factor-α and IL-17] and pathogen-associated molecular patterns.
  
  
  CONCLUSIONS
  LCs existing around or within biliary epithelial layers are important as periductal antigen-presenting cells in PBC and the migration of LCs into bile ducts is closely associated with the periductal cytokine milieu and biliary innate immunity in PBC.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimoda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Mayumi
authors.initials: M
authors.lastname: Chiba
authors.forename: Maylee
authors.initials: M
authors.lastname: Hsu
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Mio
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Xiang Shan
authors.initials: XS
authors.lastname: Ren
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohta
authors.forename: Satomi
authors.initials: S
authors.lastname: Kasashima
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kawashima
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001652:Bile Ducts / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007801:Langerhans Cells / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000503:physiopathology*; D008297:Male; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D054418:Chemokine CCL20; D016207:Cytokines; D017931:DNA Primers; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins