title: Wip1-deficient neutrophils significantly promote intestinal ischemia/reperfusion injury in mice.
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 neutrophil-dependent 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.
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: X
authors.initials: X
authors.lastname: Shen
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: B
authors.initials: B
authors.lastname: Sun
authors.forename: W
authors.initials: W
authors.lastname: Guan
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: 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. zhaoy@ioz.ac.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D020381:Interleukin-17 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000235:genetics*; D000071636:Protein Phosphatase 2C; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D010749:Phosphoprotein Phosphatases; C000607468:Ppm1d protein, mouse; D000071636:Protein Phosphatase 2C