Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cell Immunol. 2011;269(1):22-8. doi: 10.1016/j.cellimm.2011.03.005. Epub 2011 Mar 12.
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.
T 细胞免疫球蛋白和黏蛋白结构域（Tim）-3 在激活的 CD4(+)和 CD8(+)T 细胞上表达。Galectin-9 被鉴定为 Tim-3 的配体，这一发现确立了 Tim-3/galectin-9 通路，导致效应 CD4(+)和 CD8(+)T 细胞凋亡。此外，Th17 细胞是最近发现的一种 CD4(+)效应 T 细胞，在抗菌免疫中起重要作用。Tim-3/galectin-9 通路是否影响 Th17 免疫尚未阐明。本研究通过流式细胞术证实了 Tim-3 在 Th17 细胞上的表达。Th17 偏向细胞对 galectin-9 诱导的凋亡敏感。体外给予 galectin-9 可减少刺激的 Th17 细胞，并抑制 IL-17 的产生。有趣的是，肺炎克雷伯菌（K. pneumoniae）感染导致 IL-17 水平升高。重组 galectin-9 可显著减少体内的 IL-17，导致细菌清除减少和高死亡率。这些观察结果表明，Tim-3/galectin-9 通路在终止 Th17 免疫反应中起重要作用，可能是炎症性疾病的治疗靶点。
