Phenotype and influx kinetics of leukocytes and inflammatory cytokine production in kidney ischemia/reperfusion injury.

Abstract

Kidney ischemia/reperfusion (IR) injury is characterized by tubular epithelial cell (TEC) death and an inflammatory response involving cytokine production and immune cell infiltration. In various kidney diseases, increased macrophage numbers correlate with injury severity and poor prognosis. However, macrophage plasticity enables a diverse range of functions, including wound healing, making them a key target for novel therapies. This study aimed to comprehensively characterize the changes in myeloid and epithelial cells and the production of cytokines throughout the experimental IR model of acute kidney injury to aid in the identification of targets to promote and enhance kidney regeneration and repair. Flow cytometric analysis of murine unilateral IR injury was used to assess TEC and myeloid cell subpopulations in conjunction with histological analysis and cytokine production at 6h, 1, 3, 5 and 7days post IR injury, spanning the initial inflammatory phase and the following reparative phase. IR injury resulted in a rapid infiltration of Ly6Chigh monocytes and neutrophils with a steady rise in F4/80high MHCIIhigh macrophages over the injury time. The production of the inflammatory cytokines IL-6, MCP-1 and TNF coincided with an increase in IL-10 production. This characterization will provide a reference point for future studies designed to manipulate immune cell phenotype and function in order to promote endogenous repair of damaged kidneys.