• Yao Yao, Hai Deng, Pingfei Li, Jian Zhang, Junbo Zhang, Deping Wang, Songbo Li, Yixing Luo, Zhengping Wei, Guoyu Bi, Xiang-Ping Yang, and Zhao-Hui Tang.
• *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.
• Shock. 2017 Mar 1; 47 (3): 337-345.

AbstractSepsis 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.

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