title: Participation of natural killer cells in the pathogenesis of bile duct lesions in biliary atresia.
abstract: OBJECTIVE
  Immunological disturbances including innate immunity after a suspected viral infection are considered important to the pathogenesis of bile duct lesions in cases of biliary atresia (BA). In this study, we tried to evaluate whether natural killer (NK) cells and CX3CL1 (Fractalkine) and its receptor (CX3CR1) are involved in the bile duct injury.
  
  
  METHODS
  Using the section of BA (22 cases) and controls, immunohistochemistry for CD56, CD16, CD68, CX3CL1 and CX3CR1 was performed. Moreover, using cultured biliary epithelial cells (BECs) and NK cells, the production of CX3CL1 in BECs and the migration of NK cells were evaluated.
  
  
  RESULTS
  It was found that CD56(-)CD16(+)CD68(-) NK cells were increased around the damaged small and large bile ducts in BA and hepatitis C virus-related chronic hepatitis in comparison with other controls. CX3CL1 was strongly expressed on the damaged bile ducts in BA, while this expression was relatively weak or absent in the bile ducts of normal liver. The results suggest the CD56(-)CD16(+) NK cells to be involved in the development of bile duct injuries in BA. These CD16(+) NK cells were positive for CX3CR1, and attracted by CX3CL1 expressed on bile ducts. Further study revealed that stimulation with poly(I:C) (a synthetic analogue of viral dsRNA) increased the expression of CX3CL1 on cultured BECs followed by increased migrational activity of cultured NK cells.
  
  
  CONCLUSIONS
  CD56(-)CD16(+) NK cells with reduced NK activity may be involved in the bile duct damage in BA, and CD16(+) NK cells expressing CX3CR1 may be attracted by and interact with bile ducts expressing CX3CL1.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okamura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Masaki
authors.initials: M
authors.lastname: Nio
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D001656:Biliary Atresia / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D000073883:CX3C Chemokine Receptor 1; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011070:Poly I-C / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000378:metabolism; D017452:Receptors, IgG / Q000032:analysis; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D019002:CD56 Antigen; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D017077:Culture Media, Conditioned; D058851:GPI-Linked Proteins; D011070:Poly I-C; D019707:Receptors, Chemokine; D017452:Receptors, IgG; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; C428200:FCGR3B protein, human; C522918:NCAM1 protein, human