Li Duo, Guo Bin, Wu Haijing, Tan Lina, Chang Christopher, Lu Qianjin
a Department of Dermatology , Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics , Changsha , China .
Autoimmunity. 2015;48(6):353-61. doi: 10.3109/08916934.2015.1037441. Epub 2015 Apr 20.
Systemic lupus erythematosus (SLE) is a complicated autoimmune disease of multifactorial pathoaetiology. One of the most serious manifestations is lupus nephritis. The pathogenesis of SLE has not been well elucidated, but it has been reported that interleukin-17 (IL-17) and Th17 cells play important roles in the pathogenesis of SLE. IL-17A, a member of IL-17 family, amplifies the immune response by inducing the local production of chemokines and cytokines, recruiting neutrophils and monocytes, augmenting the production of autoantibodies, and aggravating the inflammation and damage of target organs such as the kidney in SLE. In recent years, several IL-17A pathway inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibody and the anti-17RA monoclonal antibody. Several agents have shown great success in Phase II trials in multiple autoimmune diseases such as psoriasis, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, and non-infectious uveitis, which has sparked the urgent need of anti-IL-17A as innovative therapeutic option in controlling disease activity of moderate-to-severe SLE. Here, we review and summarize current progress in IL-17A and SLE from in vitro studies, human expression studies, and animal models, providing novel insight into its therapeutic potential.
系统性红斑狼疮(SLE)是一种病因复杂的多因素自身免疫性疾病。最严重的表现之一是狼疮性肾炎。SLE的发病机制尚未完全阐明,但有报道称白细胞介素-17(IL-17)和Th17细胞在SLE的发病机制中起重要作用。IL-17A是IL-17家族的成员之一,通过诱导趋化因子和细胞因子的局部产生、募集中性粒细胞和单核细胞、增加自身抗体的产生以及加重SLE中肾脏等靶器官的炎症和损伤来放大免疫反应。近年来,几种IL-17A通路抑制剂已进入临床试验,包括抗IL-17A单克隆抗体和抗17RA单克隆抗体。几种药物在银屑病、类风湿性关节炎、强直性脊柱炎、多发性硬化症和非感染性葡萄膜炎等多种自身免疫性疾病的II期试验中取得了巨大成功,这引发了对将抗IL-17A作为控制中重度SLE疾病活动的创新治疗选择的迫切需求。在此,我们从体外研究、人体表达研究和动物模型方面回顾并总结了IL-17A与SLE的当前进展,为其治疗潜力提供了新的见解。