Interleukin 7 stimulates tumour necrosis factor α and Th1 cytokine production in joints of patients with rheumatoid arthritis
Interleukin 7 stimulates tumour necrosis factor α and Th1 cytokine production in joints of patients with rheumatoid arthritis
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DOI：
10.1136/ard.62.2.113
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发表时间：
2003-02-01
影响因子：
27.4
通讯作者：
Lafeber, FPJG
中科院分区：
文献类型：
--
作者：
van Roon, JAG;Glaudemans, KAFM;Lafeber, FPJG
背景：在类风湿性关节炎（RA）患者的关节中发现了大量活化的 T 细胞。白细胞介素 7 (IL7) 是一种 T 细胞生长因子，也是 Th1 和 Th2 细胞因子产生的调节剂，由 RA 患者的滑膜细胞产生。目的：探讨 RA 患者对滑液单核细胞 (SFMC) 促炎细胞因子产生的影响以及 IL7 影响 CD4+ T 细胞活性的机制。方法：在横断面组的 RA 患者中，将 IL7 水平与健康对照者进行比较并与疾病相关活动。 IL7 对细胞因子产生的影响通过 RA SFMC 和单核细胞 (MC) 存在下的 SF CD4+ T 细胞进行测试。通过酶联免疫吸附测定 (ELISA) 和单细胞 FACS 分析测量肿瘤坏死因子 α (TNFα)、IL1β、干扰素 γ (IFNgamma) 和 IL4 的产生。评估了 CD4+ T 细胞上 IL7 受体 α 链的表达（对于 IL7 信号传导至关重要）。通过细胞因子分析研究了 IL7 对分离的滑液 (SF) CD4+ T 细胞的直接影响。通过中和 MC 培养物中的 IL12，研究了 IL7 通过辅助细胞对 T 细胞的间接影响。结果：RA 患者的 IL7 血清水平高于健康对照，并且与 C 反应蛋白水平呈正相关。 IL7 刺激 SFMC 产生 TNFα，并非常有效地刺激 SF CD4+ T 细胞产生 IFNγ 和 TNFα。这些作用可能是通过 IL7 受体 α 链介导的，该链在 SF CD4+ T 细胞上大量表达。 IL7除了直接刺激T细胞细胞因子产生外，其作用部分依赖于IL12，表明IL7还刺激辅助细胞功能，导致T细胞活化。结论：IL7刺激RA患者关节内CD4+T细胞和辅助细胞产生促炎细胞因子。与疾病活动测量的相关性表明，IL7 可能对 RA 患者中 Th1 和 TNFα 介导的促炎反应的持续存在有显着贡献。
Background: A large number of activated T cells are found in the joints of patients with rheumatoid arthritis (RA). Interleukin 7 (IL7), a T cell growth factor and a regulator of Th1 and Th2 cytokine production, is produced by synoviocytes from patients with RA.Objective: To investigate the effect on proinflammatory cytokine production of synovial fluid mononuclear cells (SFMC) and the mechanism by which IL7 influences CD4+ T cell activity in patients with RA.Methods: In a cross sectional group of patients with RA, IL7 levels were compared with those of healthy controls and related to disease activity. The effect of IL7 on cytokine production was tested by RA SFMC and on SF CD4+ T cells in the presence of mononuclear cells (MC). Production of tumour necrosis factor alpha (TNFalpha), IL1beta, interferon gamma (IFNgamma), and IL4 was measured by enzyme linked immuno-sorbent assay (ELISA) and by single cell FACS analysis. Expression of the IL7 receptor alpha chain on CD4+ T cells (essential for IL7 signalling) was assessed. Direct effects of IL7 on isolated synovial fluid (SF) CD4+ T cells were studied by cytokine analysis. By neutralisation of IL12 in MC cultures, indirect effects of IL7 on T cells through accessory cells were studied.Results: IL7 serum levels were higher in patients with RA than in healthy controls and correlated positively with C reactive protein levels. IL7 stimulated TNFalpha production by SFMC and very potently stimulated IFNgamma and TNFalpha production by SF CD4+ T cells. These effects were probably mediated through the IL7 receptor alpha chain, which was abundantly expressed on SF CD4+ T cells. Besides the direct stimulation of T cell cytokine production by IL7, its action was partly dependent on IL12, indicating that IL7 also stimulates accessory cell function, leading to T cell activation.Conclusion: IL7 stimulates proinflammatory cytokine production of intra-articular CD4+ T cells and accessory cells from patients with RA. The correlation with measures of disease activity indicates that IL7 might substantially contribute to the perpetuation of Th1 and TNFalpha mediated proinflammatory responses in patients with RA.