IL-18 is essential for the development of autoimmune disease in MRL-Fas^<lpr> mice.

IL-18对于MRL-Fas^<lpr>小鼠中自身免疫性疾病的发展是必需的。

• 批准号: 13670484
• 负责人: KINOSHITA Koji
• 金额: $ 1.15万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670484/
• 关键词: Systemic lupus erythematosus; IL-18; Lupus nephritis; マウス

Many cytokines are increased in the kidneys undergoing autoimmune destruction in MRL-Fas^<lpr> mice. The specific cytokine known to initiate or promote kidney injury in MRL-Fas^<lpr> mice is IFN-γ. On the other hand, IL-18 is known to be a IFN-γ iuducible factor. Thus, to examine the impact of IL-18 on renal injury in MRL-Fas^<lpr> mice, I constructed a IL-18 receptor deficient strain. MRL-Fas^<lpr> mice lacking IL-18 receptor do not develop kidney pathology, or proteinuria, and survive longer. Intrarenal IFN-γ, IL-2, and IL-12 remained at normal levels compared with wild-type mice. IL-18 receptor deficient MRL-Fas^<lpr> mice do not develop autoantibodies and intrarenal IgG deposit. Our findings demonstrate that IL=18 is critical to pathogenesis of autoimmune lupus.

在MRL-Fas +/-小鼠中，许多细胞因子在经历自身免疫破坏的肾脏中增加<lpr>。已知在MRL-Fas +/-小鼠中引发或促进肾损伤的特异性细胞因子<lpr>是IFN-γ。另一方面，已知IL-18是IFN-γ诱导因子。因此，为了检测IL-18对MRL-Fas+小鼠中肾损伤的影响<lpr>，我构建了IL-18受体缺陷型菌株。缺乏<lpr>IL-18受体的MRL-Fas+小鼠不发生肾脏病理或蛋白尿，并且存活更长时间。与野生型小鼠相比，肾内IFN-γ、IL-2和IL-12保持在正常水平。IL-18受体缺陷型MRL-Fas^<lpr>小鼠不会产生自身抗体和肾内IgG存款。我们的研究结果表明，IL=18是至关重要的自身免疫性狼疮的发病机制。