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黏膜T细胞作为炎症性肠病的治疗靶点。

Mucosal T cells as a target for treatment of IBD.

作者信息

Watanabe Mamoru, Yamazaki Motomi, Kanai Takanori

机构信息

Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

出版信息

J Gastroenterol. 2003 Mar;38 Suppl 15:48-50.

Abstract

Interleukin-7 (IL-7) is an indispensable cytokine for the development of lymphocyte lineage cells. However, the potential role of IL-7 in peripheral nonlymphoid tissues was unclear before our study. We have demonstrated that intestinal epithelial cells produce IL-7 and that IL-7 serves as a regulatory factor for proliferation of mucosal lymphocytes expressing IL-7 receptor (IL-7R). Recent studies demonstrated that intestinal epithelial cell-derived IL-7 plays a crucial role in the organization of mucosal lymphoid tissues and regulating the normal immune response in intestinal mucosa. In a previous study, we demonstrated that IL-7 transgenic mice developed chronic colitis. Here, we have demonstrated the essential role of mucosal IL-7/IL-7R-dependent signals in the development of chronic intestinal inflammation. Our results indicate that mucosal IL-7/IL-7R-dependent signals are involved in the development of chronic intestinal inflammation in both the mouse model and human disease of the intestinal mucosa. Therefore, current studies indicate that therapeutic approaches by specific targeting of IL-7R-expressing mucosal T cells may be feasible in the treatment of human ulcerative colitis.

摘要

白细胞介素-7(IL-7)是淋巴细胞谱系细胞发育所必需的细胞因子。然而,在我们的研究之前,IL-7在周围非淋巴组织中的潜在作用尚不清楚。我们已经证明,肠道上皮细胞可产生IL-7,并且IL-7作为表达IL-7受体(IL-7R)的黏膜淋巴细胞增殖的调节因子。最近的研究表明,肠道上皮细胞衍生的IL-7在黏膜淋巴组织的组织形成以及调节肠道黏膜中的正常免疫反应中起关键作用。在先前的一项研究中,我们证明IL-7转基因小鼠会发展为慢性结肠炎。在此,我们证明了黏膜IL-7/IL-7R依赖性信号在慢性肠道炎症发展中的重要作用。我们的结果表明,黏膜IL-7/IL-7R依赖性信号参与了小鼠模型和人类肠道黏膜疾病中慢性肠道炎症的发展。因此,目前的研究表明,通过特异性靶向表达IL-7R的黏膜T细胞的治疗方法在治疗人类溃疡性结肠炎中可能是可行的。

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