The roles of cytokines on the development of rheumatoid arthritis

我们建立了携带HTLV-I(HTLV-I TG)和IL-1受体拮抗剂基因敲除(IL-1Ra KO)小鼠的转基因小鼠，并发现这些小鼠自发地发生了自身免疫性关节炎。此外，我们已经报道了T细胞依赖性细胞免疫在疾病的发展中起着至关重要的作用。在这个项目中，我们使用这两个小鼠模型评估了细胞因子在自身免疫性关节炎发生发展中的作用。我们发现IL-1和IL-6在HTLV-ITG疾病的发生发展中起关键作用，而IL-1Ra KO小鼠的疾病需要肿瘤坏死因子-α。与其他细胞因子不同，IL-17已知由活化的CD4T细胞产生，并诱导其他细胞因子和趋化因子。此外，它还被认为与人类类风湿性关节炎有关，因为这种细胞因子在患者的关节中被检测到。然后，我们建立了IL-17基因敲除(IL-17 KO)小鼠，并发现IL-17缺陷完全抑制了IL-1Ra KO小鼠的疾病。

We have produced transgenic mice carrying tax gene of HTLV-I (HTLV-I Tg) and IL-1 receptor antagonist knockout (IL-1Ra KO) mice, and found these mice spontaneously develop autoimmune arthritis. Also, we have reported that T cell dependent cellular immunity is crucial for the development of the disease. In this project, we evaluated that the roles of cytokine on the development of the autoimmune arthritis using those 2 mouse models. We showed that IL-1 and IL-6 is crucial for the development of the disease of HTLV-I Tg and TNF-a is required in the disease of IL-1Ra KO mice. Unlike other cytokines, IL-17 is known to be produced by the activated CD4 T cells, and induces other cytokines and chemokines. Also, it is suggested to be involved in rheumatoid arthritis in humans, because this cytokine is detected in the joints of the patients. Then, we produced IL-17 knockout (IL-17 KO) mice, and found that IL-17 deficiency completely suppresses the disease in the IL-1Ra KO mice.