Preliminary study on immunologic mechanism of chemokine receptor CXCR3 and its ligands involved in mouse fulminant hepatitis / 中华微生物学和免疫学杂志

ABSTRACT

Objective To investigate the role of the chemokine receptor CXCR3 and its ligands in the migration of lymphocytes and acute hepatic failure. Methods BALB/cJ mice (6-8 weeks, female) were intraperitoneally injected with 100 PFU mouse hepatitis virus-3(MHV-3). The proportions and numbers of T cells and NK cells in liver, spleen, and blood as well as the expression of CXCR3 in T cells, and NK cells post MHV-3 infection was analyzed by flow cytometry. The hepatic mRNA level of the CXCR3-associated chemokines(CXCL9 and CXCL10) was detected by real-time PCR. A transwell migration assay was used to assess the chemotactic effect of MHV-3-infected hepatocytes and CXCL10 on the splenic lymphocytes. Results Following MHV-3 infection, the number of hepatic NK cells and T cells and the frequencies of hepatic NK cells and T cells expressing CXCR3 increased markedly; however, in the spleen and peripheral blood, they both decreased significantly. Moreover, the hepatic mRNAs levels of CXCL9 and CXCL10 were significantly elevated post infection. The transwell migration assay demonstrated that MHV-3-infected hepatocytes have the capacity to attract and recruit the splenic NK cells and T cells, and CXCL10 plays a key role in lymphocyte mobilization from the spleen. Conclusion Interactions between CXCR3 and its ligands (CXCL9 and CXCL10),especially CXCL10 may play a key role in the recruitment of intrahepatic lymphocytes and subsequent necroinflammation and acute hepatic failure in MHV-3 infection.