Ischemia reperfusion injury modulates the expression of TIGIT ligands, CD115 and CD112 and co-signaling molecules, CD226 and PD1 in mouse kidney 2912

Abstract Description Ischemia reperfusion (IR) injury increases T cell immunoreceptor with Ig and ITIM domains (TIGIT) on kidney T cells that participate in the pathogenesis of acute kidney injury (AKI) in mice. We investigated the effects of IR injury on TIGIT interacting ligands (CD155, CD112, CD113) and co-signaling molecules (CD226, CD96, PD1). Male C57BL6 mice underwent bilateral kidney IR surgery. TIGIT ligand expression was measured with western blotting at 24h and 18 days post-IR. TIGIT ligands and co-signaling partners were assessed at baseline and 24h post-IR using flow cytometry. Western blotting showed enhanced expression of CD155 (5.6±0.5 fold) and CD112 (2.4±0.5 fold) 24h after AKI. Flow analysis showed increased CD155 (1.5±0.3 vs 26.7±4.7%; P < 0.0001) and CD112 (1.5±0.3 vs 26.7±4.7%; P < 0.0001) expression in CD11b+ cells at 24h compared to control. TIGIT co-stimulatory counterpart CD226 decreased in CD4 (67.1±19.0 vs 46.0±10.3%; P < 0.05), double negative (DN) (92.1±5.1 vs 61.4±10.8%; P < 0.001) and NKT (91.2±3.5 vs 71.2±5.9%; P < 0.001) cells at 24h. TIGIT+ cells expressed PD1 both at baseline and after IR injury in CD4, CD8 and DN T cells. PD1 significantly (P < 0.01) increased at 24h in TIGIT+ CD4, CD8 and DN T cells compared to TIGIT- cells. IR injury increased CD155 and CD112 and decreased co-signaling CD226 expression. TIGIT and PD1 are co-expressed by a subset of kidney T cells. TIGIT ligands and co-signaling partners are promising targets for IR injury to kidney and other organs. Funding Sources This work was supported by NIH/NIDDK grants R01DK132278 and R01DK123342 to SN and HR, respectively. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)