Costimulatory molecule VSIG4 exclusively expressed on macrophages alleviates renal tubulointerstitial injury in VSIG4 KO mice

Abstract

Background: Activation and infiltration of T cells and macrophages are key features of renal tubulointerstitial injury. The costimulatory molecule V-set and immunoglobulin domain-containing protein-4 (VSIG4), which is exclusively expressed on macrophages, is capable of inhibiting the T cell response. However, it is unclear whether VSIG4 is involved in renal tubulointerstitial injury. This study was designed to investigate the role of VSIG4 in renal tubulointerstitial injury and the related T cell infiltration.

Methods: The unilateral ureteric obstruction (UUO) model of renal inflammation and tubulointerstitial fibrosis was established in VSIG4 transgenic knock-out C57BL/6 mice (VSIG4(-/-)) and wild-type C57BL/6 mice (VSIG4(+/+)). Comparative analysis of renal biological indices were assessed by quantitative real-time PCR and immunofluorescence staining.

Results: Both the VSIG4(-/-) and VSIG4(+/+) mice showed UUO-related temporal changes in renal expression of CD3, CD4 and CD8 T cell markers, with the protein levels being significantly lower in the VSIG4(+/+) UUO mice. Moreover, at each time point examined the UUO VSIG4(+/+) mice showed significantly lower renal mRNA levels of the cytokines interleukin (IL)-2, interferon- and tumor necrosis factor-, but significantly higher IL-10, than the UUO VSIG4(-/-) mice.

Conclusions: The macrophage-expressed VSIG4 may act to alleviate renal tubulointerstitial injury via inhibition of T cell infiltration and secretion of inflammation related factors.