Galectin-9 ameliorates Con A-induced hepatitis by inducing CD4(+)CD25(low/int) effector T-Cell apoptosis and increasing regulatory T cell number.
Galectin-9 ameliorates Con A-induced hepatitis by inducing CD4(+)CD25(low/int) effector T-Cell apoptosis and increasing regulatory T cell number.
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DOI：
10.1371/journal.pone.0048379
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Suo Q
中科院分区：
文献类型：
--
作者：
Lv K;Zhang Y;Zhang M;Zhong M;Suo Q
T细胞介导的肝损伤是许多慢性人类肝病发病机制中的关键事件，例如肝移植排斥、原发性胆汁性肝硬化和硬化性胆管炎。我们和其他研究小组之前曾报道，半乳糖凝集素 9（一种 β-半乳糖苷结合动物凝集素）可能可用于治疗 T 细胞介导的疾病。为了评估半乳糖凝集素9（galectin-9）对小鼠刀豆球蛋白A（Con A）诱导的肝炎的直接作用并阐明其机制，我们将半乳糖凝集素9（galectin-9）注射到小鼠体内，并评估其对Con A诱导的肝炎的治疗效果。 Galectin-9 静脉注射。在 Con A 注射前 30 分钟给 Balb/c 小鼠注射。与未治疗相比，galectin-9 预处理显着降低了血清 ALT 和 AST 水平，改善了肝脏组织病理学，表明肝炎得到改善。这种治疗效果不仅归因于 Th1 免疫反应减弱，还归因于调节性 T 细胞数量增加，如 CD4+CD25low/int 效应 T 细胞凋亡显着增加和促炎细胞因子水平降低所反映。我们的研究结果构成了第一个临床前数据，表明干扰体内 TIM-3/galectin-9 信号传导可以改善 Con A 诱导的肝炎。这一策略可能代表了一种治疗涉及 T 细胞激活的人类疾病的新治疗方法。
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 β-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. 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. Our findings constitute the first preclinical data indicating that interfering with TIM-3/galectin-9 signaling in vivo could ameliorate Con A-induced hepatitis. This strategy may represent a new therapeutic approach in treating human diseases involving T cell activation.
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DOI：
10.1084/jem.179.5.1529
发表时间：
1994-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mizuhara H;O'Neill E;Seki N;Ogawa T;Kusunoki C;Otsuka K;Satoh S;Niwa M;Senoh H;Fujiwara H
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Fujiwara H
DOI：
10.4049/jimmunol.0903435
发表时间：
2010-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Boenisch O;D'Addio F;Watanabe T;Elyaman W;Magee CN;Yeung MY;Padera RF;Rodig SJ;Murayama T;Tanaka K;Yuan X;Ueno T;Jurisch A;Mfarrej B;Akiba H;Yagita H;Najafian N
通讯作者：
Najafian N
影响因子：
82.9
作者：
Kondo, T;Suda, T;Nagata, S
通讯作者：
Nagata, S
影响因子：
13.5
作者：
MORITA, M;WATANABE, Y;AKAIKE, T
通讯作者：
AKAIKE, T
影响因子：
15.9
作者：
TIEGS, G;HENTSCHEL, J;WENDEL, A
通讯作者：
WENDEL, A