Kanai Takanori, Nemoto Yasuhiro, Kamada Nobuhiko, Totsuka Teruji, Hisamatsu Tadakazu, Watanabe Mamoru, Hibi Toshifumi
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Curr Opin Gastroenterol. 2009 Jul;25(4):306-13. doi: 10.1097/MOG.0b013e32832bc627.
This review focuses on CD4+ T cells involved in the mediation of inflammatory tissue damage in murine models of inflammatory bowel diseases (IBDs). In particular, we describe the distinct roles of the homeostatic cytokine IL-7, which is essential to the maintenance of colitogenic memory CD4+ cells, and the newly discovered effector cytokine IL-17. We also discuss the close correlation between colitogenic Th17-type CD4+ T cells and inducible CD4+CD25+Foxp3+ regulatory T cells.
IBDs are characterized by wasting and chronic intestinal inflammation induced by many different cytokine-mediated pathways. It is clearly recognized that medical and surgical interventions do not cure Crohn's disease because relapse is the rule after remission. Until a few years ago, IBD was classified into Th1-dependent, that is, Crohn's disease, and Th2-dependent, that is, ulcerative colitis, phenotypes. However, in recent years, it has been shown that new T-cell subclasses, that is, Th17 and regulatory T cells (T(R)), exist independently of Th1 and Th2 and that they play a central role in modulating IBD.
The persistence of IL-7-dependent colitogenic memory CD4+ T cells is critical to the maintenance of experimental colitis. On the other hand, though Th1 and Th2 colitogenic memory CD4+ cells exist, in recent years the central role of IL-17-producing Th17-type cells in IBD has attracted renewed interest. The development of molecularly targeted therapies aimed at a variety of different Th-dependent pathogenic mechanisms may represent a novel approach to IBD therapy.
本综述聚焦于参与炎症性肠病（IBD）小鼠模型中炎症组织损伤介导过程的CD4 + T细胞。特别地，我们描述了稳态细胞因子IL - 7的独特作用，其对于致结肠炎记忆CD4 +细胞的维持至关重要，以及新发现的效应细胞因子IL - 17。我们还讨论了致结肠炎Th17型CD4 + T细胞与诱导性CD4 + CD25 + Foxp3 +调节性T细胞之间的密切相关性。
IBD的特征是由多种不同细胞因子介导的途径所诱导的消瘦和慢性肠道炎症。人们清楚地认识到，药物和手术干预并不能治愈克罗恩病，因为缓解后复发是常态。直到几年前，IBD被分为Th1依赖型，即克罗恩病，和Th2依赖型，即溃疡性结肠炎，两种表型。然而，近年来已表明，新的T细胞亚类，即Th17和调节性T细胞（T（R）），独立于Th1和Th2而存在，并且它们在调节IBD中起核心作用。
依赖IL - 7的致结肠炎记忆CD4 + T细胞的持续存在对于实验性结肠炎的维持至关重要。另一方面，虽然存在Th1和Th2致结肠炎记忆CD4 +细胞，但近年来，产生IL - 17的Th17型细胞在IBD中的核心作用引起了新的关注。针对多种不同Th依赖的致病机制开发分子靶向疗法可能代表了一种治疗IBD的新方法。
