Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis
Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis
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DOI：
10.4049/jimmunol.171.3.1556
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发表时间：
2003-08-01
影响因子：
4.4
通讯作者：
Watanabe, M
中科院分区：
文献类型：
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作者：
Yamazaki, M;Yajima, T;Watanabe, M
IL-7/IL-7R依赖性信号通路在调节肠粘膜免疫反应中发挥着至关重要的作用。在这里，我们证明了该途径在慢性结肠炎的发展和治疗中的关键作用。在TCR α链敲除小鼠和IL-7转基因小鼠的慢性发炎粘膜中，表达高水平IL-7R的T细胞大量浸润。将表达高水平 IL-7R 的粘膜 T 细胞（而不是表达低水平 IL-7R 的 T 细胞）从这些小鼠转移到重组酶激活基因 2(-/-) 小鼠中诱导慢性结肠炎。通过施用少量毒素偶联的抗 IL-7R 抗体，选择性消除表达高水平 IL-7R 的 T 细胞，可完全改善已形成的、正在进行的结肠炎。这些发现证明，针对表达高水平 IL-7R 的粘膜 T 细胞的治疗方法可有效治疗慢性肠道炎症，并且可能可用于治疗人类炎症性肠病。
The IL-7/IL-7R-dependent signaling pathway plays a crucial role in regulating the immune response in intestinal mucosa. Here we demonstrate the pivotal role of this pathway in the development and treatment of chronic colitis. T cells expressing high levels of IL-7R were substantially infiltrated in the chronic inflamed mucosa of TCR alpha-chain knockout mice and IL-7 transgenic mice. Transfer of mucosal T cells expressing high levels of IL-7R, but not T cells expressing low levels of IL-7R, from these mice into recombinase-activating gene-2(-/-) mice induced chronic colitis. Selective elimination of T cells expressing high levels of IL-7R by administrating small amounts of toxin-conjugated anti-IL-7R Ab completely ameliorated established, ongoing colitis. These findings provide evidence that therapeutic approaches targeting mucosal T cells expressing high levels of IL-7R are effective in the treatment of chronic intestinal inflammation and may be feasible for use in the therapy of human inflammatory bowel disease.