The N-and C-terminal carbohydrate recognition domains of galectin-9 contribute differently to its multiple functions in innate immunity and adaptive immunity

摘要：

　　By binding to T cell (1)g mucin-3 (Tim-3) expressed on different cells,galectin-9 (Gal-9) mediates two important functions,triggering T cell death and activating innate immune cells.The mechanisms by which ligation of the same molecule on different cell types mediates different effects are largely unclear.Gal-9 contains two carbohydrate recognition domains (CRD) in the N-and C-terminal regions (Gal-9-N and Gal-9-c).The N and C terminals of Gal-9 have been shown to have different activities in promoting T cell death.However,whether the differences between two domains account for its dual functions remains to be elucidated.Here we hypothesized that the different functions of Gal-9 in innate immunity and adaptive immunity are mediated by different domains,To test this,we created recombinant Gal-9 (Gal-9-NC) and homodimers containing either the NCRD (Gal-9-N) or the CCRD (Gal-9-C).All these Gal-9 constructs can activate dendritic cells (DCs) and induce T cell death.However,the Gal-9-C was much more potent than the Gal-9-N in inducing T cell death,while the Gal-9-N was much more effective in activating DCs by inducing much higher TNF-α and IL-6 production,greater phosphorylation of p38 and AKT.in both DC and T cells,Gal-9-N but not Gal-9-C stimulation resulted in markedly iκBα degradation.Finally,computer analyses suggested different patterns and affinities for the binding of the Gal-9-N and Gal-9-C to their receptor,Tim-3.Our data suggest that the N-and C-terminal CRDs of Gal-9 contribute differently to its ability to induce T cell death and to activate DCs.Further investigations on the underlying mechanisms will provide new insights into the biochemical basis for the multiple activities of Gal-9.

关键词： Galectin-9 CRD Innate immunity Adaptive immunity

作者: Yurong Li Hui Peng Gencheng Han Beifen Shen Yan Li Jiannan Feng Shaoxia Geng Shusheng Geng Huawei Wei Guojiang Chen Xinying Li Liyan Wang Renxi Wang

作者单位: Department of Molecular Immunology, Institute of Basic Medical Sciences,Beijing 100850, China Department of Molecular Immunology, Institute of Basic Medical Sciences,Beijing 100850, China ; Inst Beijing Tian Guang Shi Biorech Corp.Ltd.Beijing Economic-Technological Development Area, Beijing 100

会议类型: 国际会议

会议名称: The 6th International Conference of Molecular Simulations and Applied Informatics Technologies(第六届国际分子模拟与信息技术应用学术会议(ICMS&I))

会议地点: 南京

会议语种:英文

页码: 497-504

在线出版日期: 2012-05-13（万方平台首次上网日期，不代表论文的发表时间）