galectin-9 ameliorates con a-induced hepatitis by inducing cd4+cd25lowint effector t-cell apoptosis and increasing regulatory t cell numbercd4 + cd25lowint galectin-9改善con a-induced肝炎诱导效应t细胞凋亡、增加调节性t细胞数量.pdfVIP

Galectin-9 Ameliorates Con A-Induced Hepatitis by Inducing CD4+CD25low/int Effector T-Cell Apoptosis and Increasing Regulatory T Cell Number 1 . 2. 1 1 1 Kun Lv * , Yingying Zhang , Mengying Zhang , Min Zhong , Qifeng Suo 1 Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, People’s Republic of China, 2 Laboratory Medcine of Yijishan Hospital, Wannan Medical College, Wuhu, People’s Republic of China Abstract Background: T cell-mediated liver damage is a key event in the pathogenesis of many chronic human liver diseases, such as liver transplant rejection, primary biliary cirrhosis, and sclerosing cholangitis. We and other groups have previously reported that galectin-9, one of the b-galactoside binding animal lectins, might be potentially useful in the treatment of T cell- mediated diseases. To evaluate the direct effect of galectin-9 on hepatitis induced by concanavalin A (Con A) administration in mice and to clarify the mechanisms involved, we administered galectin-9 into mice, and evaluated its therapeutic effect on Con A-induced hepatitis. Methodology/Principal Findings: Galectin-9 was administrated i.v. to Balb/c mice 30 min before Con A injection. Compared with no treatment, galectin-9 pretreatment significantly reduced serum ALT and AST levels and improved liver histopathology, suggesting an ameliorated hepatitis. This therapeutic effect was not only attributable to a blunted Th1 immune response, but also to an increased number in regulatory T cells, as reflected in a significantly increased apoptosis of CD4+CD25low/int effector T cells and in reduced proinflammatory cytokine levels. Conclusion/Significance: Our findings constitute the first preclini