The Role of CXCR3 in the Induction of Primary Biliary Cirrhosis

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.