Introduction: In kidney transplantation, antibody-mediated rejection severely compromises the long-term function of allografts. At present, there are no effective methods to prevent and treat the occurrence and progression of antibody mediated rejection, and exploring new therapeutic interventions is a major challenge.
Method: The skin of BALB/c mice was transplanted to the back of C57BL/6 mice for pre-sensitization. A week later, we transplanted the kidneys of BALB/c mice into C57BL/6 mice to construct an kidney transplant antibody-mediated rejection(AMR) model. Kidneys from C57BL/6 mice were transplanted into unsensitized C57BL/6 mice to serve as a control group. The expression of Donor-Specific Antibody(DSA) and CXCL10 in peripheral blood of mice in two groups were detected. The AMR group were treated with CXCL10 neutralizing antibody and CXCR3 monoclonal antibody. The kidney function, the degree of rejection and the degree of macrophage infiltration were observed.
Results: DSA and CXCL10 in peripheral blood of the recipient mice were significantly increased in AMR group. Immunofluorescence Staining and Histopathology showed that C4d staining positive and obvious macrophage infiltration in the AMR group. After blocking CXCL10-CXCR3, in the AMR group, early allograft macrophage infiltration was significantly reduced; Graft antibody mediated rejection was alleviated and graft renal function was improved.
Conclusion: Targeting the CXCL10-CXCR3 axis mitigates antibody mediated kidney transplant rejection in mice. It is a promising approach to reduce clinical antibody-mediated rejection of kidney transplantation.