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:(Y. Zhao), Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beichen West Road 1-5, Chaoyang District, Beijing 100101, China.
Keywords:Intestinal ischemia/reperfusion injury, neutrophils, IL-17A, Wip1.
Abstract: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.
