title: Tim-3 signaling pathway as a novel negative mediator in lipopolysaccharide-induced endotoxic shock.
abstract: Sepsis is a complex clinical condition caused by a dysregulated immune response to an infection. However, the mechanism by which our immune system controls this amplified inflammation is largely unknown. In this study, we investigated whether Tim-3 pathway could serve as a negative mediator in lipopolysaccharide (LPS)-induced endotoxic shock. Our results showed that Tim-3 was expressed on CD4(+) T cells, CD8(+) T cells, and NK cells, and was significantly increased in the peritoneal cavity of septic mice. Tim-3 acted as a marker of immune exhaustion and Tim-3-positive T cells and NK cells had a lower interferon (IFN)-γ production. Furthermore, blockade of Tim-3 pathway significantly accelerated mortality in septic mice, while activation of this pathway prolonged survival time. In vitro administration of Tim-3 blocking antibody restored the release of IFN-γ from splenocytes and decreased splenocyte apoptosis, and increased levels of IFN-γ and tumor necrosis factor (TNF)-α were also detected in septic mice at 24h post in vivo administration of the antibody. In contrast, activation of Tim-3 pathway prevented cell proliferation. Thus, Tim-3 signaling pathway acts as a novel negative mediator in LPS-induced endotoxic shock and could be a potential therapeutic target for the treatment of sepsis.
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lingqing
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Munanie
authors.initials: M
authors.lastname: Jane
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yaowu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: tjszyong@163.com.
authors.forename: Ziyong
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004195:Disease Models, Animal; D037161:Galectins / Q000096:biosynthesis / Q000494:pharmacology; D000072597:Hepatitis A Virus Cellular Receptor 2; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012772:Shock, Septic / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D011991:Receptors, Virus; C508186:galectin 9, mouse; D007371:Interferon-gamma