Tim-3 Negatively Mediates Natural Killer Cell Function in LPS-induced Endotoxic Shock

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Oct 23

PMID 25337993

Citations 13

Authors

Hongyan Hou

Weiyong Liu

Shiji Wu

Yanjun Lu

Jing Peng

Yaowu Zhu

Yanfang Lu

Feng Wang

Ziyong Sun

Affiliations

Soon will be listed here.

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.

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