CXCR3 alleviates renal ischemia-reperfusion injury via increase of Tregs

Increasing evidence has demonstrated that regulatory T cells (Tregs) suppress innate immunity, as well as protect the kidneys from ischemia-reperfusion injury (IRI) and offer a potentially effective strategy to prevent or alleviate renal IRI. The present study explored whether C-X-C motif chemokine receptor 3 (CXCR3) alleviated renal IRI by increasing Tregs. Male C57BL/6J mice were divided into sham-surgery, IRI, CXCR3 overexpression (OE-CXCR3)+IRI, PC61+IRI and OE-CXCR3+PC61+IRI groups. Histopathological examination of the kidney was carried out using hematoxylin-eosin and Masson staining. The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Blood and kidney levels of IL-6, TNF-alpha, C-C motif chemokine ligand (CCL)-2 and IL-10 were detected by ELISA and western blotting. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in kidney tissues were also measured to assess oxidative stress. The population of Tregs in the kidney was assessed using flow cytometry. The results demonstrated that administration of OE-CXCR3 to IRI mice significantly decreased the levels of Scr, BUN, IL-6, TNF-alpha, CCL-2 and MDA, increased the levels of IL-10, SOD and GSH-Px, and mitigated the morphologic injury and fibrosis induced by IR compared with the IRI group. In addition, administration of OE-CXCR3 induced significant reductions in the expression levels of fibrosis-related markers, including fibronectin and type IV collagen, and increased the number of Tregs. These roles of OE-CXCR3 were significantly neutralized following deletion of Tregs with PC61 (anti-CD25 antibody). Together, the present study demonstrated that injection of OE-CXCR3 lentiviral vectors into animal models can alleviate renal IRI by increasing the number of Tregs. The results may be a promising approach for the treatment of renal IRI.