title: Tim-3 ligand galectin-9 reduces IL-17 level and accelerates Klebsiella pneumoniae infection.
abstract: T cell immunoglobulin and mucin domain (Tim)-3 is expressed on activated CD4(+) and CD8(+) T cells. Identification of galectin-9 as a ligand for Tim-3 has now firmly established the Tim-3/galectin-9 pathway, which results in apoptosis of effector CD4(+) and CD8(+) T cells. Moreover, Th17 cells are a recently discovered CD4(+) effector T cell, which are important in antimicrobial immunity. Whether the Tim-3/galectin-9 pathway affects Th17 immunity has not been elucidated. Here, we demonstrated expression of Tim-3 on Th17 cells by flow cytometry. Th17-skewed cells were sensitive to galectin-9-induced apoptosis. In vitro administration of galectin-9 decreased stimulated Th17 cells and inhibited production of IL-17. Interestingly, Klebsiella pneumoniae (K. pneumoniae) infection led to enhanced IL-17 levels. Recombinant galectin-9 significantly decreased IL-17 in vivo, which resulted in reduced bacterial clearance and high mortality. These observations suggest that the Tim-3/galectin-9 pathway plays an important role in termination of Th17-immune responses, and could be a therapeutic target for inflammatory diseases.
authors: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Feng
authors: F
authors: Wang
authors: Jie
authors: J
authors: Xu
authors: Yalong
authors: Y
authors: Liao
authors: Yue
authors: Y
authors: Wang
authors: Cailin
authors: C
authors: Liu
authors: Xuhui
authors: X
authors: Zhu
authors: Zhonghua Klaus
authors: ZK
authors: Chen
authors: Zhiyong
authors: Z
authors: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D037161:Galectins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D020381:Interleukin-17 / Q000378:metabolism*; D007710:Klebsiella Infections / Q000276:immunology / Q000401:mortality / Q000503:physiopathology*; D007711:Klebsiella pneumoniae; D008024:Ligands; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism*
chemical_list: D037161:Galectins; D020381:Interleukin-17; D008024:Ligands; D019717:Tissue Inhibitor of Metalloproteinase-3; C508186:galectin 9, mouse