title: The role of CXCR3 in the induction of primary biliary cirrhosis.
abstract: OBJECTIVE
  Investigate whether CXCR3 and its ligands were involved in the pathogenesis of primary biliary cirrhosis (PBC) in an autoimmune cholangitis animal model.
  
  
  METHODS
  Female C57BL/6 mice were injected with 5 mg/kg of poly I:C intraperitoneally twice a week for 24 weeks. PBC model was confirmed by liver function, serum autoantibodies and liver biopsy. Lymphocytes subsets in liver and spleen and CXCL10 serum level were tested by flow cytometry and ELISA. Liver specimens were collected to evaluate the differences in pathology between WT and CXCR3(-/-) mice.
  
  
  RESULTS
  Antimitochondrial antibody was detected in all PBC model. Numbers of infiltrates were detected in the portal areas 8 weeks after poly I:C injection, which progressed up to 24 weeks. Compared to control mice, CXCL10 serum level increased in PBC mice and the proportion of CXCR3(+) cells increased in the intrahepatic infiltrates of PBC mice, chiefly on CD8(+) cells, whereas the expression of CXCR3 on CD3(+) and CD8(+) splenocytes decreased in PBC model. Compared with WT mice, CXCR3(-/-) mice developed delayed and milder progression of cellular inflammation.
  
  
  CONCLUSIONS
  CXCR3 might contribute to the development of PBC in murine model. Knockout of CXCR3 might delay and alleviate the PBC disease progression, but could not entirely block the disease development.
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Fei
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D002761:Cholangitis / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008099:Liver / Q000276:immunology / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D054367:Receptors, CXCR3 / Q000235:genetics / Q000502:physiology*
chemical_list: D001323:Autoantibodies; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3