Title:Wip1-Deficient Neutrophils Significantly Promote Intestinal Ischemia/Reperfusion Injury in Mice
Volume: 15
Issue: 1
Author(s): J. Du, X. Shen, Y. Zhao, X. Hu, B. Sun, W. Guan, S. Li and Y. Zhao
Affiliation:
关键词:
肠缺血/再灌注损伤，中性粒细胞，IL-17A，Wip1。
摘要: Wip1 is a serine/threonine protein phosphatase which plays a critical role in
neutrophil development and maturation. In the present study, we used a neutrophildependent
model of intestinal ischemia/reperfusion (I/R) injury to identify the role of Wip1
in neutrophil function under the condition of oxidative stress and inflammation. Wip1-
deficient mice displayed more severe intestinal I/R injury with increased infiltration of
neutrophils and higher expression of chemokines like CXCL-1, CXCL-2 and CCL-2, as
well as inflammatory cytokine like TNF-α and IL-17. Studies in Wip1KOa→WT full
hematopoietic chimera mice showed that Wip1 intrinsically regulated the function of
immune cells after intestinal I/R injury. Through adoptive transfer of neutrophils from WT
mice or mice with deficiency of IL-17, IL-17/Wip1 or Wip1, we demonstrated that Wip1KO neutrophils produced
more IL-17 and eventually led to more severe intestinal I/R injury. Thus, our findings identify Wip1 as an
intrinsic negative regulator of neutrophil inflammation in intestinal I/R injury process.
