Interleukin-35 is upregulated in systemic sclerosis and its serum levels are associated with early disease
Interleukin-35 is upregulated in systemic sclerosis and its serum levels are associated with early disease
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DOI：
10.1093/rheumatology/kev260
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发表时间：
2015-12-01
期刊：
影响因子：
5.5
通讯作者：
Senolt, Ladislav
中科院分区：
文献类型：
--
作者：
Tomcik, Michal;Zerr, Pawel;Senolt, Ladislav
目标。 IL-35 是 IL-12 家族的成员，由 p35/IL-12a 和 EBI3/IL-27b 亚基组成。 IL-35 在实验和人类自身免疫炎症条件下发挥免疫调节活性。我们的目的是评估 SSc 患者皮肤和循环中的 IL-35 表达，并表征其与 SSc 相关特征的潜在关联。方法。通过定量 PCR、免疫组织化学和免疫荧光对皮肤和真皮成纤维细胞中 IL-35 的表达进行定量。在 40 名 SSc 患者中测量了 IL-35（通过 ELISA）、CRP（通过比浊法）、ANA（通过免疫荧光）和 ENA 复合物自身抗体（通过免疫印迹）的血清水平。在 40 名年龄和性别匹配的健康对照中测定血清 IL-35。结果。 SSc 皮肤和真皮成纤维细胞中 IL-35 的表达以 TGF-β 依赖性方式增加。 IL-35 诱导静息成纤维细胞激活表型并增强胶原蛋白的释放。与健康对照相比，SSc 患者的 IL-35 血清水平升高 [中位数 83.9（四分位距 45.1-146.1）vs 36.2（四分位距 17.2-49.4）pg/ml，P < 0.0001]。血清IL-35与病程呈负相关（r=-0.4339，P=0.0052）。与这一发现一致，与活动性和晚期 SSc 模式的患者相比，毛细管镜检查评估中早期 SSc 模式患者的血清 IL-35 升高。结论。本研究表明 IL-35 在 SSc 皮肤、真皮成纤维细胞和血清中过度表达。 TGF-β 诱导 IL-35，进而激活静息成纤维细胞并增强胶原蛋白的释放，从而导致 SSc 中异常的 TGF-β 信号传导。血清 IL-35 升高与 SSc 的早期炎症阶段相关。
Objectives. IL-35 is a member of the IL-12 family consisting of p35/ IL-12a and EBI3/ IL-27b subunits. IL-35 exerts immunomodulatory activities in experimental and human autoimmune inflammatory conditions. Our aim was to assess IL-35 expression in the skin and circulation of SSc patients and to characterize its potential association with SSc-related features.Methods. Expression of IL-35 in skin and dermal fibroblasts was quantified by quantitative PCR, immunohistochemistry and immunofluorescence. Serum levels of IL-35 (by ELISA), CRP (by turbidimetry), ANA (by immunofluorescence) and autoantibodies of the ENA complex (by immunoblot) were measured in 40 SSc patients. Serum IL-35 was determined in 40 age- and sex-matched healthy controls.Results. IL-35 expression was increased in SSc skin and dermal fibroblasts in a TGF-beta-dependent manner. IL-35 induced an activated phenotype in resting fibroblasts and enhanced the release of collagen. IL-35 serum levels were increased in patients with SSc compared with healthy controls [median 83.9 (interquartile range 45.1-146.1) vs 36.2 (interquartile range 17.2-49.4) pg/ml, P < 0.0001]. Serum IL-35 was negatively correlated with disease duration (r = -0.4339, P = 0.0052). In line with this finding, serum IL-35 was increased in patients with an early SSc pattern on capillaroscopy assessment compared with those with active and late SSc patterns.Conclusion. The present study demonstrates overexpression of IL-35 in SSc skin, dermal fibroblasts and serum. TGF-beta induces IL-35, which in turn activates resting fibroblasts and enhances the release of collagen, thereby contributing to aberrant TGF-beta signalling in SSc. Increased serum IL-35 is associated with early, inflammatory stages of SSc.