Abstract
Sepsis is an exaggerated inflammatory condition response to different microorganisms with high mortality rates and extremely poor prognosis. Natural killer (NK) cells have been reported to be the major producers of IFN-γ and key players in promoting systematic inflammation in lipopolysaccharide (LPS)-induced endotoxic shock. T-cell immunoglobulin and mucin domain (Tim)-3 pathway has been demonstrated to play an important role in the process of sepsis, however, the effect of Tim-3 on NK cell function remains largely unknown. In this study, we observed a dynamic inverse correlation between Tim-3 expression and IFN-γ production in NK cells from LPS-induced septic mice. Blockade of the Tim-3 pathway could increase IFN-γ production and decrease apoptosis of NK cells in vitro, but had no effect on the expression of CD107a. Furthermore, NK cell cytotoxicity against K562 target cells was enhanced after blocking Tim-3 pathway. In conclusion, our results suggest that Tim-3 pathway plays an inhibitory role in NK cell function, which might be a potential target in modulating the excessive inflammatory response of LPS-induced endotoxic shock.
Highlights
Sepsis is characterized by an exaggerated systemic inflammatory response mainly caused by lipopolysaccharide (LPS) of Gramnegative bacterium, leading to serious effects such as multi-organ failure and even death [1]
Our previous data have suggested that T-cell immunoglobulin and mucin domain (Tim)-3 signaling pathway serves as a novel negative mediator in the development of sepsis and that the expression of Tim-3 is increased on Natural killer (NK) cells [20]
We further determined the effect of Tim-3 on NK cell function during the development of sepsis
Summary
Sepsis is characterized by an exaggerated systemic inflammatory response mainly caused by lipopolysaccharide (LPS) of Gramnegative bacterium, leading to serious effects such as multi-organ failure and even death [1]. The overwhelming release of proinflammatory cytokines, in particular TNF-a and IFN-c, are involved in the development of sepsis [2]. Previous studies have indicated that macrophages, neutrophils and conventional T cells are activated and contribute to the sepsis-induced systemic inflammatory response [3]. Natural killer (NK) cells, which have been identified as the major producers of IFN-c, play a central role in the pathogenesis of sepsis. Depletion of NK cells provides protection against LPS or multi-bacteria-induced sepsis in mice [4,5,6]
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