Department of Medicine (463), Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525GA Nijmegen, The Netherlands.
Infect Immun. 2011 Nov;79(11):4681-7. doi: 10.1128/IAI.05242-11. Epub 2011 Sep 6.
Interleukin-23 (IL-23) is known to play a crucial role in the development and maintenance of T helper 17 cells. It has been previously demonstrated that IL-17 is involved in experimental Lyme arthritis, caused by Borrelia burgdorferi bacteria. However, the precise role of the IL-23 receptor (IL-23R) for the B. burgdorferi-induced IL-17 responses or human Lyme disease has not yet been elucidated. IL-23R single nucleotide polymorphism (SNP) rs11209026 was genotyped using the TaqMan assay. Functional studies were performed using peripheral blood mononuclear cells, and cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Dose-dependent production of IL-23 and IL-17 by B. burgdorferi could be observed. Interestingly, when IL-23 bioactivity was inhibited by a specific antibody against IL-23p19, IL-17 production was significantly downregulated. In contrast, production of gamma interferon (IFN-γ) was not affected after the blockade of IL-23 activity. Moreover, individuals bearing a single nucleotide polymorphism in the IL-23R gene (Arg381Gln) produced significantly less IL-17 after B. burgdorferi stimulation compared with that of the individuals bearing the wild type. Despite lower IL-17 production, the IL-23R gene polymorphism did not influence the development of chronic Lyme disease in a cohort of patients with Lyme disease. This study demonstrates that IL-23R signaling is needed for B. burgdorferi-induced IL-17 production in vitro and that an IL-23R gene SNP leads to impaired IL-17 production. However, the IL-23R gene polymorphism is not crucial for the pathogenesis of chronic Lyme.
白细胞介素-23（IL-23）已知在 T 辅助 17 细胞的发育和维持中发挥关键作用。先前已经证明，IL-17 参与了由伯氏疏螺旋体细菌引起的实验性莱姆关节炎。然而，IL-23 受体（IL-23R）在伯氏疏螺旋体诱导的 IL-17 反应或人类莱姆病中的确切作用尚未阐明。使用 TaqMan 测定法对 IL-23R 单核苷酸多态性（SNP）rs11209026 进行基因分型。使用外周血单核细胞进行功能研究，并使用酶联免疫吸附测定（ELISA）测量细胞因子。可以观察到伯氏疏螺旋体的 IL-23 和 IL-17 产生呈剂量依赖性。有趣的是，当用针对 IL-23p19 的特异性抗体抑制 IL-23 生物活性时，IL-17 的产生明显下调。相反，阻断 IL-23 活性后，γ干扰素（IFN-γ）的产生不受影响。此外，与携带野生型的个体相比，IL-23R 基因（Arg381Gln）中的单核苷酸多态性的个体在伯氏疏螺旋体刺激后产生的 IL-17 明显减少。尽管 IL-17 的产生较低，但 IL-23R 基因多态性并未影响莱姆病患者队列中慢性莱姆病的发展。这项研究表明，IL-23R 信号传导对于伯氏疏螺旋体诱导的体外 IL-17 产生是必需的，并且 IL-23R 基因 SNP 导致 IL-17 产生受损。然而，IL-23R 基因多态性对于慢性莱姆病的发病机制并不重要。
