title: Reovirus type-2-triggered autoimmune cholangitis in extrahepatic bile ducts of weanling DBA/1J mice.
abstract: BACKGROUND
  Reovirus is a proposed cause of infantile biliary atresia. However, mechanistic insight regarding Reo-2 as a potential cholangiotropic virus is lacking. Furthermore, it is unknown whether Reo-2 infection can induce autoimmune-mediated bile duct injury.
  
  
  METHODS
  Lesions of bile ducts in newborn DBA/1J mice infected with Reo-2 were analyzed immunopathologically.
  
  
  RESULTS
  Damage to biliary epithelia occurs after Reo-2 infection. In addition, nonsuppurative cholangitis with fibrosis in extrahepatic (especially septal) bile ducts developed following complete viral clearance from the liver. At the inflamed ducts, major histocompatibility complex class I expressing((+)) and FAS(+) cholangiocytes were associated with FAS ligand(+) lymphocytes and tumor necrosis factor-α(+) mononuclear cells (macrophages and lymphocytes). These cholangiocytes were apoptotic and necrotic. Moreover, affected ducts were infiltrated by CD3(+), CD4(+), CD8(+), IFN-γ(+), and FAS(+) lymphocytes. Analysis of blood from Reo-2-infected mice revealed that they developed anticholangiocyte cytoplasm antibodies and had high serum IFN-γ concentration. Notably, there was no increase in Foxp3(+) lymphocytes at inflamed ducts, lymph nodes, and thymi.
  
  
  CONCLUSIONS
  Reo-2 infection induced T-helper cell type 1-dependent injury to bile ducts in weanling mice. The lesions observed in mice may be analogous to those associated with human infantile biliary atresia, which are caused by an autoimmune-mediated process.
authors.affiliation: Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nakashima
authors.affiliation: Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Tomoeda
authors.affiliation: Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshino
authors.affiliation: Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Mizuno
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001324:Autoantigens / Q000097:blood; D001327:Autoimmune Diseases / Q000821:virology*; D017734:Bile Ducts, Extrahepatic / Q000473:pathology* / Q000648:ultrastructure; D002761:Cholangitis / Q000821:virology*; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008099:Liver / Q000201:enzymology; D051379:Mice; D008811:Mice, Inbred DBA; D030102:Orthoreovirus, Mammalian / Q000472:pathogenicity* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000097:blood; D014779:Virus Replication
chemical_list: D001324:Autoantigens; D020381:Interleukin-17; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D007371:Interferon-gamma; D000469:Alkaline Phosphatase