Kanai Takanori, Watanabe Mamoru
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Graduate School of Medicine, 1-5-45 Yushima, Tokyo 113-8519, Japan.
Expert Opin Biol Ther. 2005 Apr;5(4):451-62. doi: 10.1517/14712598.5.4.451.
As our understanding of the immunological and genetic basis of inflammatory bowel disease (IBD) grows, potential therapeutic options are being developed at a rapid pace. Nevertheless, new drugs for IBD are needed because about half of all patients with severe ulcerative colitis (UC) eventually undergo colectomy, and a significant part of Crohn's disease (CD) patients do not respond to standard medical therapies, including immunosuppressants and TNF-alpha neutralising antibodies, or suffer from significant side effects. Finally, recurrence of disease activity following remission is frequent in both UC and CD, and there is an unmet need for effective maintenance strategies. It is well-known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only does active suppression by regulatory T (TR) cells play an important role in the normal intestinal homeostasis, but also its dysregulation might lead to the development of IBD. TR cells are functional subsets of T cells that downregulate adaptive immune responses by interfering with the activation of dendritic cells and proliferation of T cells. From experimental work it is now clear that TR cells play a critical role in maintaining immune homeostasis, and several therapeutic approaches have been targeted at the induction of TR cells in order to control mucosal inflammation. Before using TR cells clinically as living immunosuppressants for the treatment of IBD, however, we have to pass many critical checkpoints, such as the in vitro expansion of TR cells and the confirmation of their safety. This paper will discuss recently gained knowledge of human TR cells and the possibility of their clinical usages as a new strategy for the treatment of IBD.
随着我们对炎症性肠病（IBD）免疫和遗传基础的理解不断深入，潜在的治疗选择正迅速涌现。然而，仍需要治疗IBD的新药，因为约一半的重度溃疡性结肠炎（UC）患者最终会接受结肠切除术，并且相当一部分克罗恩病（CD）患者对包括免疫抑制剂和肿瘤坏死因子-α中和抗体在内的标准药物治疗无反应，或出现严重的副作用。最后，UC和CD患者在缓解后疾病活动复发都很常见，并且对有效的维持策略存在未满足的需求。众所周知，肠道中的免疫反应处于可控炎症状态，这表明不仅调节性T（TR）细胞的主动抑制在正常肠道稳态中起重要作用，而且其失调可能导致IBD的发生。TR细胞是T细胞的功能亚群，通过干扰树突状细胞的活化和T细胞的增殖来下调适应性免疫反应。从实验工作中现在很清楚，TR细胞在维持免疫稳态中起关键作用，并且已经有几种治疗方法旨在诱导TR细胞以控制黏膜炎症。然而，在将TR细胞作为活的免疫抑制剂临床用于治疗IBD之前，我们必须通过许多关键关卡，例如TR细胞的体外扩增及其安全性的确认。本文将讨论最近获得的关于人类TR细胞的知识以及将其临床应用作为治疗IBD新策略的可能性。
