白细胞介素 17A 和白细胞介素 17F 在类风湿关节炎和外周脊柱关节炎中的表达和功能反应。
Interleukin 17A and IL-17F Expression and Functional Responses in Rheumatoid Arthritis and Peripheral Spondyloarthritis.
机构信息
S. Chen, MD, PhD, Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, University of Amsterdam, Amsterdam, Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands, and Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
I.C. Blijdorp, BSc, T.E. Latuhihin, BSc, N.G. Yeremenko, PhD, Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, University of Amsterdam, Amsterdam, and Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
出版信息
J Rheumatol. 2020 Nov 1;47(11):1606-1613. doi: 10.3899/jrheum.190571. Epub 2020 Jan 15.
OBJECTIVE
Targeting the interleukin 17 (IL-17) axis is efficacious in psoriasis and spondyloarthritis (SpA), but not in rheumatoid arthritis (RA). We investigated potential differences in tissue expression and function of IL-17A and IL-17F in these conditions.
METHODS
mRNA expression of cytokines and their receptors was assessed by quantitative PCR in psoriasis skin samples, in SpA and RA synovial tissue (ST) samples and in fibroblast-like synoviocytes (FLS). Cytokines were measured in synovial fluid (SF) and FLS supernatants by ELISA. FLS were stimulated with IL-17A or IL-17F cytokines supplemented with tumor necrosis factor (TNF), or with pooled SF from patients with SpA or RA.
RESULTS
Levels of ( = 0.031) and ( = 0.017) mRNA were lower in psoriatic arthritis ST compared to paired psoriasis skin samples. The level of mRNA was 2.7-fold lower than that of IL-17F in skin ( = 0.0078), but 17.3-fold higher in ST ( < 0.0001). In SF, the level of IL-17A protein was 37.4-fold higher than that of IL-17F [median 292.4 (IQR 81.4-464.2) vs median 7.8 (IQR 7.7-8.7) pg/mL; < 0.0001]. IL-17A and IL-17F mRNA and protein levels did not differ in SpA compared to RA synovitis samples, and neither were the IL-17 receptors and , or the TNF receptors and , differentially expressed between SpA and RA ST, nor between SpA and RA FLS. SpA and RA FLS produced similar amounts of IL-6 and IL-8 protein upon stimulation with IL-17A or IL-17F cytokines, supplemented with 1 ng/ml TNF. Pooled SpA or RA SF samples similarly enhanced the inflammatory response to IL-17A and IL-17F simulation in FLS.
CONCLUSION
The IL-17A/IL-17F expression ratio is higher in SpA synovitis compared to psoriasis skin. Expression of IL-17A and IL-17F, and the functional response to these cytokines, appear to be similar in SpA and RA synovitis.
目的
靶向白细胞介素 17（IL-17）轴在银屑病和脊柱关节炎（SpA）中是有效的，但在类风湿关节炎（RA）中则不然。我们研究了这些疾病中 IL-17A 和 IL-17F 的组织表达和功能的潜在差异。
方法
通过定量 PCR 评估银屑病皮肤样本、SpA 和 RA 滑膜组织（ST）样本和成纤维样滑膜细胞（FLS）中细胞因子及其受体的 mRNA 表达。通过 ELISA 测量滑液（SF）和 FLS 上清液中的细胞因子。用 TNF 补充的 IL-17A 或 IL-17F 细胞因子或来自 SpA 或 RA 患者的混合 SF 刺激 FLS。
结果
与配对的银屑病皮肤样本相比，银屑病关节炎 ST 中 （=0.031） 和 （=0.017） 的 mRNA 水平较低。在皮肤中， （=0.0078），但在 ST 中， （=0.0001），IL-17F 的 mRNA 水平比 IL-17A 低 2.7 倍。在 SF 中，IL-17A 蛋白水平比 IL-17F 高 37.4 倍[中位数 292.4（IQR 81.4-464.2）比中位数 7.8（IQR 7.7-8.7）pg/mL；<0.0001]。与 RA 滑膜炎样本相比，SpA 中 IL-17A 和 IL-17F 的 mRNA 和蛋白水平没有差异，SpA 和 RA ST 之间也没有差异表达的 IL-17 受体 和 ，或 TNF 受体 和 ，也没有差异表达的 IL-17 受体 和 ，或 TNF 受体 和 ，在 SpA 和 RA FLS 之间。用 1ng/ml TNF 补充的 IL-17A 或 IL-17F 细胞因子刺激后，SpA 和 RA FLS 产生的 IL-6 和 IL-8 蛋白量相似。来自 SpA 或 RA 的混合 SF 样本同样增强了 FLS 对 IL-17A 和 IL-17F 模拟的炎症反应。
结论
与银屑病皮肤相比，SpA 滑膜炎中 IL-17A/IL-17F 的表达比例更高。在 SpA 和 RA 滑膜炎中，IL-17A 和 IL-17F 的表达以及对这些细胞因子的功能反应似乎相似。
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