title: α-Lactose Improves the Survival of Septic Mice by Blockade of TIM-3 Signaling to Prevent NKT Cell Apoptosis and Attenuate Cytokine Storm.
abstract: Sepsis is the leading cause of death among critically ill patients and natural killer T (NKT) cell activation is essential to induce inflammatory cytokine cascade in sepsis. However, little is known about what regulates the NKT cell function during sepsis. Herein, we showed that T-cell immunoglobulin and mucin domain 3 (Tim-3) expression in NKT cells is elevated in experimental mice during sepsis. Tim-3 expression was positively correlated with NKT cell activation and apoptosis. In sepsis, interleukin (IL)-12 secreted by dendritic cell exposure to lipopolysaccharide increased the expression of Tim-3 in NKT cells. Administration of α-lactose to block Tim-3 signaling pathway significantly improved the survival of septic mice, concomitant with reduced IL-12 production by dendritic cells, reduced Tim-3 expression, prevented NKT cell apoptosis, and attenuated production of inflammatory cytokines. Collectively, Tim-3 signaling in NKT cells plays a critical role in the immunopathogenesis of sepsis. Thus, α-lactose could be a promising immunomodulatory agent in the treatment of sepsis.
authors: *Division of Trauma Surgery, Department of Surgery, Tongji Hospital, Wuhan, China †Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Yao
authors: Y
authors: Yao
authors: Hai
authors: H
authors: Deng
authors: Pingfei
authors: P
authors: Li
authors: Jian
authors: J
authors: Zhang
authors: Junbo
authors: J
authors: Zhang
authors: Deping
authors: D
authors: Wang
authors: Songbo
authors: S
authors: Li
authors: Yixing
authors: Y
authors: Luo
authors: Zhengping
authors: Z
authors: Wei
authors: Guoyu
authors: G
authors: Bi
authors: Xiang-Ping
authors: XP
authors: Yang
authors: Zhao-Hui
authors: ZH
authors: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D018664:Interleukin-12 / Q000378:metabolism; D007785:Lactose / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000187:drug effects*; D018805:Sepsis / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D018664:Interleukin-12; D007785:Lactose