Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle.
Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle.
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DOI：
10.1371/journal.pone.0002629
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发表时间：
2008-07-09
期刊：
影响因子：
3.7
通讯作者：
Sturm A
中科院分区：
文献类型：
--
作者：
Paclik D;Danese S;Berndt U;Wiedenmann B;Dignass A;Sturm A
半乳糖凝集素-4是属于半乳糖凝集素家族的碳水化合物结合蛋白。在这里，我们提供了新的证据表明，半乳糖凝集素-4选择性地表达和分泌的肠上皮细胞和有效地结合到激活的外周和粘膜固有层的T细胞的CD 3表位。半乳糖凝集素-4在CD 3表位处的碳水化合物依赖性结合是完全功能性的，并且抑制T细胞活化、循环和扩增。半乳糖凝集素-4通过钙蛋白酶依赖性途径诱导活化的外周和粘膜固有层T细胞凋亡，而不是半胱天冬酶依赖性途径。通过反义寡核苷酸阻断半乳糖凝集素-4可减少TNF-α抑制剂诱导的T细胞死亡，这为其在调节T细胞功能中的重要作用提供了进一步的证据。此外，在T细胞中，半乳糖凝集素-4减少促炎细胞因子分泌，包括IL-17。在实验性结肠炎模型中，半乳糖凝集素-4改善粘膜炎症，诱导粘膜T细胞凋亡并减少促炎细胞因子的分泌。我们的研究结果表明，半乳糖凝集素-4在肠道中发挥着独特的作用，并分配一个新的作用，这种蛋白质在控制肠道炎症的选择性诱导T细胞凋亡和细胞周期的限制。总而言之，在定义了其生物学作用后，我们提出半乳凝素-4是一种新型抗炎剂，可以对T细胞扩增和细胞凋亡紊乱的疾病（例如炎症性肠道疾病）具有治疗效果。
Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully functional and inhibited T cell activation, cycling and expansion. Galectin-4 induced apoptosis of activated peripheral and mucosal lamina propria T cells via calpain-, but not caspase-dependent, pathways. Providing further evidence for its important role in regulating T cell function, galectin-4 blockade by antisense oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore, in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL-17. In a model of experimental colitis, galectin-4 ameliorated mucosal inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction. Conclusively, after defining its biological role, we propose Galectin-4 is a novel anti-inflammatory agent that could be therapeutically effective in diseases with a disturbed T cell expansion and apoptosis such as inflammatory bowel disease.
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影响因子：
3
作者：
Huflejt, ME;Leffler, H
通讯作者：
Leffler, H
影响因子：
29.4
作者：
Colombel, Jean-Frederic;Sandborn, William J.;Pollack, Paul F.
通讯作者：
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影响因子：
4.8
作者：
Chen, M;Won, DJ;Gottlieb, RA
通讯作者：
Gottlieb, RA
影响因子：
3.1
作者：
Grabig, A.;Paclik, D.;Sturm, A.
通讯作者：
Sturm, A.
影响因子：
4.8
作者：
Matarrese, P;Tinari, A;Malorni, W
通讯作者：
Malorni, W