Department of Rheumatology & Clinical Immunology, UMC Utrecht, Heidelberglaan 100, Utrecht, PO Box 85500 F02,127 3508 GA, The Netherlands.
Arthritis Res Ther. 2012 Jun 7;14(3):R137. doi: 10.1186/ar3870.
We sought to investigate the capacity of interleukin (IL)-7 to enhance collagen-induced arthritis and to study by what mechanisms this is achieved.
Mice received multiple injections with IL-7 or phosphate-buffered saline (PBS) as a control. Arthritis severity and incidence were determined by visual examination of the paws. Joint destruction was determined by assessing radiographs and immunohistochemistry of the ankle joints. Total cellularity and numbers of T-cell and B-cell subsets were assessed, as well as ex vivo production of interferon-γ (IFN-γ), IL-17, and IL-4. Proinflammatory mediators were measured in serum with multianalyte profiling.
IL-7 increased arthritis severity and radiology-assessed joint destruction. This was consistent with IL-7-increased intensity of cell infiltrates, bone erosions, and cartilage damage. Splenic CD19+ B cells and CD19+/GL7+ germinal center B cells, as well as CD4 and CD8 numbers, were increased by IL-7. IL-7 expanded memory T cells, associated with increased percentages of IFN-γ-, IL-4-, and IL-17-producing CD4+ T cells. On antigen restimulation of draining lymph node cells in vitro IL-7 treatment was found to increase IFN-γ and IL-17 production, whereas IL-4 was reduced. IL-7 also increased concentrations of proinflammatory mediators, indicative of T-cell activation (sCD40L), vascular activation (VCAM-1, VEGF), tissue destruction (fibroblast growth factor-basic (FGF-b), LIF), and chemotaxis (MIP-1γ, MIP-3β, lymphotactin, MDC, and MCP-5).
In arthritic mice, IL-7 causes expansion of T and B cells, associated with increased levels of proinflammatory mediators. IL-7 intensifies arthritis severity and joint destruction, accompanied by increased Th1 and Th17 activity. These data indicate that IL-7 could be an important mediator in arthritic conditions and that targeting IL-7 or its receptor represent novel therapeutic strategies.
我们旨在研究白细胞介素（IL）-7 增强胶原诱导性关节炎的能力，并研究其实现的机制。
小鼠接受 IL-7 或磷酸盐缓冲盐水（PBS）多次注射作为对照。通过检查爪子来确定关节炎的严重程度和发生率。通过评估踝关节的 X 光片和免疫组织化学来确定关节破坏。评估总细胞数以及 T 细胞和 B 细胞亚群的数量，以及体外产生的干扰素-γ（IFN-γ）、IL-17 和 IL-4。使用多分析物分析测定血清中的促炎介质。
IL-7 增加了关节炎的严重程度和 X 光评估的关节破坏。这与 IL-7 增加细胞浸润、骨侵蚀和软骨损伤的强度一致。脾 CD19+B 细胞和 CD19+/GL7+生发中心 B 细胞以及 CD4 和 CD8 数量均被 IL-7 增加。IL-7 扩大了记忆 T 细胞，与 IFN-γ-、IL-4-和 IL-17-产生的 CD4+T 细胞的百分比增加有关。在体外引流淋巴结细胞的抗原再刺激中，发现 IL-7 处理增加了 IFN-γ 和 IL-17 的产生，而 IL-4 减少。IL-7 还增加了促炎介质的浓度，表明 T 细胞活化（sCD40L）、血管活化（VCAM-1、VEGF）、组织破坏（碱性成纤维细胞生长因子-b（FGF-b）、LIF）和趋化性（MIP-1γ、MIP-3β、淋巴毒素、MDC 和 MCP-5）。
在关节炎小鼠中，IL-7 导致 T 和 B 细胞的扩增，与促炎介质水平升高相关。IL-7 加重关节炎的严重程度和关节破坏，伴随着 Th1 和 Th17 活性的增加。这些数据表明，IL-7 可能是关节炎疾病的重要介质，靶向 IL-7 或其受体代表新的治疗策略。
