FGF2 cooperates with IL-17 to promote autoimmune inflammation.

FGF2 cooperates with IL-17 to promote autoimmune inflammation.
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FGF2与IL-17协同促进自身免疫炎症

DOI:
10.1038/s41598-017-07597-8
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发表时间:
2017-08-01
期刊:
影响因子:
4.6
通讯作者:
Qian Y
Qian Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shao X;Chen S;Yang D;Cao M;Yao Y;Wu Z;Li N;Shen N;Li X;Song X;Qian Y

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IL-17是一种促炎细胞因子,与多种自身免疫性疾病有关。我们最近报道,在葡聚糖硫酸钠(DSS)诱导的结肠炎中,FGF2与IL-17协同作用对肠上皮起保护作用。在这里,我们报告了FGF2-IL-17协同作用在自身免疫性关节炎发病机制中的致病作用。联合应用FGF2和IL-17可协同诱导人滑膜内膜成纤维样滑膜细胞ERK的激活以及细胞因子和趋化因子的产生。此外,FGF2在小鼠关节中的异位表达增强了IL-17诱导的组织中炎性细胞因子和趋化因子的产生。在胶原诱导性关节炎(CIA)模型中,虽然在体内异位表达FGF2会加剧野生型对照组的组织炎症和疾病症状,但在IL17A−/−小鼠中这种作用基本上是钝化的。综上所述,我们的研究提示,FGF2与IL-17协同作用,通过协同IL-17诱导炎症反应,促进自身免疫性关节炎的发病。
IL-17 is a pro-inflammatory cytokine implicated a variety of autoimmune diseases. We have recently reported that FGF2 cooperates with IL-17 to protect intestinal epithelium during dextran sodium sulfate (DSS)-induced colitis. Here, we report a pathogenic role of the FGF2-IL-17 cooperation in the pathogenesis of autoimmune arthritis. Combined treatment with FGF2 and IL-17 synergistically induced ERK activation as well as the production of cytokines and chemokines in human synovial intimal resident fibroblast-like synoviocytes (FLS). Furthermore, ectopic expression of FGF2 in mouse joints potentiated IL-17-induced inflammatory cytokine and chemokine production in the tissue. In the collagen-induced arthritis (CIA) model, while ectopic expression of FGF2 in vivo exacerbated tissue inflammation and disease symptom in the wild-type controls, the effect was largely blunted in Il17a −/− mice. Taken together, our study suggests that FGF2 cooperates with IL-17 to promote the pathogenesis of autoimmune arthritis by cooperating with IL-17 to induce inflammatory response.
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