title: IL-17A-producing NK cells were implicated in liver injury induced by ischemia and reperfusion.
abstract: NK cells play a critical role in several types of liver injury. The aim of this study was to evaluate the role of NK cells in liver ischemia reperfusion injury (IRI) and the underlying mechanism. Male Rag1-/- mice and wild type mice were subjected to partial hepatic IRI. Anti-NK1.1 (300 μg/mouse, ip) was used to deplete NK cells. Liver injury was evaluated by level of serum alanine aminotransferase (ALT). Hepatic inflammatory cytokines, neutrophils and CXCL-2 expression were measured following ischemia and reperfusion. Additionally, NK cells were cultured with or without IL-6, IL-21, IL-23 and IL-10 for 24h, then IL-17A level in the supernatants was analyzed by ELISA. Production of IL-17A was increased in NK cells after reperfusion. Various cytokines such as, IL-6, IL-21 and IL-23, which also elevated after IRI, can promote IL-17A production and up-regulate the phosphorylation of STAT3 in NK cells, while the increase was repressed in the presence of IL-10. Depletion of NK cells decreased IL-17A level in Rag1-/- mice ischemic lobes. Meanwhile, hepatic infiltration of neutrophils and CXCL-2 level were reduced and liver injury was ameliorated. Neutralization of IL-17A was used to confirm the role of this cytokine produced by NK cells in Rag1-/- mice. In conclusion, at initial stage of liver IRI, NK cells increase IL-17A production and promote liver injury.
authors.affiliation: Department of Liver Transplantation, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Li
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Qian
authors.forename: Ye
authors.initials: Y
authors.lastname: Fan
authors.forename: Xingli
authors.initials: X
authors.lastname: Huang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000098:blood supply / Q000276:immunology / Q000293:injuries*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D018398:Homeodomain Proteins; C556062:IL10 protein, mouse; C098680:Il17a protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; C064658:RAG-1 protein; D016753:Interleukin-10; D000098546:Interleukin-21