Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis
Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis
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DOI：
10.1002/eji.200636658
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发表时间：
2006-11-01
影响因子：
5.4
通讯作者：
Bachmann, Martin F.
中科院分区：
文献类型：
--
作者：
Roehn, Till A.;Jennings, Gary T.;Bachmann, Martin F.
白细胞介素 17 是一种 T 细胞衍生的细胞因子，可诱导多种细胞类型释放促炎介质。最近，描述了与 Th1 和 Th2 细胞不同的产生 IL-17 的 T 辅助细胞 (Th17) 的子集，它构成了新的 T 细胞极化状态。异常的 Th17 反应和 IL-17 的过度表达与许多自身免疫性疾病有关，包括类风湿性关节炎和多发性硬化症。阻断 IL-17 的分子（例如 IL-17 特异性单克隆抗体）已被证明可有效改善动物模型中的疾病。迄今为止，针对 IL-17 的主动免疫是一种未经尝试的方法。在此，我们探索使用与重组 IL-17 (IL-17-VLP) 缀合的病毒样颗粒进行主动免疫来中和 IL-17 的潜力。用IL-17-VLP免疫诱导高水平的抗IL-17抗体，从而克服自然耐受性，即使在不添加佐剂的情况下也是如此。在胶原诱导的关节炎和实验性自身免疫性脑脊髓炎中，用 IL-17-VLP 免疫的小鼠的疾病发生率较低，疾病进展较慢，并且疾病严重程度得分降低。因此，针对IL-17的主动免疫代表了治疗慢性炎症性疾病的一种新的治疗方法。
Interleukin 17 is a T cell-derived cytokine that induces the release of pro-inflammatory mediators in a wide range of cell types. Recently, a subset of IL-17-producing T helper cells (Th17) distinct from Th1 and Th2 cells has been described, which constitutes a new T cell polarization state. Aberrant Th17 responses and overexpression of IL-17 have been implicated in a number of autoimmune disorders including rheumatoid arthritis and multiple sclerosis. Molecules blocking IL-17 such as IL-17-specific monoclonal antibodies have proved to be effective in ameliorating disease in animal models. Hitherto, active immunization targeting IL-17 is an untried approach. Herein we explore the potential of neutralizing IL-17 by active immunization using virus-like particles conjugated with recombinant IL-17 (IL-17-VLP). Immunization with IL-17-VLP induced high levels of anti-IL-17 antibodies thereby overcoming natural tolerance, even in the absence of added adjuvant. Mice immunized with IL-17-VLP had lower incidence of disease, slower progression to disease and reduced scores of disease severity in both collagen-induced arthritis and experimental autoimmune encephalomyelitis. Active immunization against IL-17 therefore represents a novel therapeutic approach for the treatment of chronic inflammatory diseases.