IL-33 is required for kidney ischemia-reperfusion-induced injury in mice

Abstract

Abstract Introduction Ischemia-reperfusion (IR) injury during kidney transplantation induces necrosis of renal cells and the release of “alarmins” such as IL-33 that can activate the innate immune system, thereby triggering an inflammatory response and tissue damage leading to renal failure, dysfunction or rejection. The aim of this study was to investigate the contribution of IL-33 in kidney IR injury. Methods 10–12-week-old wild-type (WT) and IL-33-deficient (IL-33Gt/Gt) male C57/Bl6 mice were subjected to 32 minutes of unilateral kidney ischemia or a Sham operation. After 24 hours, kidneys were harvested and leucocyte infiltration (macrophages, neutrophils, NK and NKT cells) was analyzed by flow cytometry. Renal injury was assessed by measurement of plasma creatinine and histological grading. Results Plasma creatinine level and tissue damage significantly increased after renal IR in WT mice, as compared with Sham-operated animals, a difference that disappeared when WT mice were replaced by IL-33Gt/Gt mice. Even though intra-renal neutrophil (CD11b(+)GR-1(+)) were significantly increased 24 hour-post IR in both WT and IL-33Gt/Gt mice, this phenomenon was found to be significantly attenuated in IL-33Gt/Gt mice. Moreover, monocyte/macrophages (CD11b(+)F4/80(+)) and NKT cells, also known for their deleterious effect during renal IR injury, seemed to be less recruited 24 hour-post IR in IL-33Gt/Gt mice compared with WT mice. Conclusion IL-33Gt/Gt mice are less sensitive to kidney damage 24 hour-post IR, consistent with a deleterious effect of IL-33 during renal IR injury. This study underlines a new possible role of IL-33 as an innate-immune mediator during kidney IR injury.