Department of Biomedical Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Infect Immun. 2013 Dec;81(12):4421-30. doi: 10.1128/IAI.01129-13. Epub 2013 Sep 16.
Previous studies have shown that cells and cytokines associated with interleukin-17 (IL-17)-driven inflammation are involved in the arthritic response to Borrelia burgdorferi infection. Here, we report that IL-17 is a contributing factor in the development of Lyme arthritis and show that its production and histopathological effects are regulated by interleukin-10 (IL-10). Spleen cells obtained from B. burgdorferi-infected, "arthritis-resistant" wild-type C57BL/6 mice produced low levels of IL-17 following stimulation with the spirochete. In contrast, spleen cells obtained from infected, IL-10-deficient C57BL/6 mice produced a significant amount of IL-17 following stimulation with B. burgdorferi. These mice developed significant arthritis, including erosion of the bones in the ankle joints. We further show that treatment with antibody to IL-17 partially inhibited the significant hind paw swelling and histopathological changes observed in B. burgdorferi-infected, IL-10-deficient mice. Taken together, these findings provide additional evidence of a role for IL-17 in Lyme arthritis and reveal an additional regulatory target of IL-10 following borrelial infection.
先前的研究表明,与白细胞介素-17(IL-17)驱动的炎症相关的细胞和细胞因子参与了伯氏疏螺旋体感染引起的关节炎反应。在这里,我们报告说 IL-17 是莱姆关节炎发展的一个促成因素,并表明其产生和组织病理学效应受到白细胞介素-10(IL-10)的调节。从伯氏疏螺旋体感染的“关节炎抗性”野生型 C57BL/6 小鼠中获得的脾细胞在受到螺旋体刺激后产生低水平的 IL-17。相比之下,从感染的 IL-10 缺陷型 C57BL/6 小鼠中获得的脾细胞在受到伯氏疏螺旋体刺激后产生大量的 IL-17。这些小鼠出现了明显的关节炎,包括踝关节骨骼的侵蚀。我们进一步表明,用抗 IL-17 抗体治疗部分抑制了在感染伯氏疏螺旋体的 IL-10 缺陷型小鼠中观察到的显著后爪肿胀和组织病理学变化。综上所述,这些发现为 IL-17 在莱姆关节炎中的作用提供了额外的证据,并揭示了伯氏疏螺旋体感染后 IL-10 的另一个调节靶点。