Prolonged, granulocyte-macrophage colony-stimulating factor-dependent, neutrophil survival following rheumatoid synovial fibroblast activation by IL-17 and TNFalpha.
Prolonged, granulocyte-macrophage colony-stimulating factor-dependent, neutrophil survival following rheumatoid synovial fibroblast activation by IL-17 and TNFalpha.
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在类风湿滑膜滑膜成纤维细胞激活IL-17和TNFALPHA后，长时间的粒细胞巨噬细胞刺激性刺激因子依赖性，中性粒细胞存活。
DOI：
10.1186/ar2406
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发表时间：
2008
影响因子：
4.9
通讯作者：
Buckley, Christopher D.
中科院分区：
文献类型：
--
作者：
Parsonage, Greg;Filer, Andrew;Bik, Magdalena;Hardie, Debbie;Lax, Sian;Howlett, Katherine;Church, Leigh D.;Raza, Karim;Wong, See-Heng;Trebilcock, Emily;Scheel-Toellner, Dagmar;Salmon, Mike;Lord, Janet M.;Buckley, Christopher D.
类风湿性关节炎炎性浸润的一个令人惊讶的特征是中性粒细胞在滑液内和血管翳软骨边界处的积聚。最近的研究结果表明，IL-17分泌的T辅助细胞（TH 17细胞）的一个独特的子集在连接免疫反应的适应性和先天性臂和调节中性粒细胞稳态中起着关键作用。因此，我们测试了这样的假设，即滑膜成纤维细胞通过在用IL-17激活后产生中性粒细胞存活因子来桥接将TH 17细胞与中性粒细胞连接的生物反应。共聚焦显微镜和流式细胞术分别检测类风湿性滑膜中IL-17表达细胞和外周血及滑液中IL-17表达细胞。将外周血中性粒细胞与类风湿性关节炎滑膜成纤维细胞（RASF）或预先暴露于重组人IL-17、TNFα或两种细胞因子组合的RASF条件培养基共培养。收获中性粒细胞，并在通过流式细胞术计数之前用活体线粒体染料3，3 '-二己基氧碳菁碘化物染色。发现表达TH 17的CD 4+细胞在类风湿性滑膜组织和类风湿性关节炎滑液中积累。用IL-17和TNFα处理的RASF（RASFIL-17/TNF）有效地使共培养的中性粒细胞的功能寿命加倍。这完全是由于成纤维细胞分泌的可溶性因子。从RASFIL-17/TNF条件培养基中特异性消耗粒细胞-巨噬细胞集落刺激因子表明，这种细胞因子约占中性粒细胞存活活性的一半。磷脂酰肌醇-3-激酶和NF-κB通路的抑制表明RASFIL-17/TNF介导的中性粒细胞拯救中需要两种信号通路。在类风湿性滑膜微环境中发现的具有延长寿命的中性粒细胞数量增加部分归因于滑膜成纤维细胞的IL-17和TNFα活化。类风湿性滑膜内表达TH 17的T细胞可能对这种作用有显著贡献。
A surprising feature of the inflammatory infiltrate in rheumatoid arthritis is the accumulation of neutrophils within synovial fluid and at the pannus cartilage boundary. Recent findings suggest that a distinct subset of IL-17-secreting T-helper cells (TH17 cells) plays a key role in connecting the adaptive and innate arms of the immune response and in regulating neutrophil homeostasis. We therefore tested the hypothesis that synovial fibroblasts bridge the biological responses that connect TH17 cells to neutrophils by producing neutrophil survival factors following their activation with IL-17. IL-17-expressing cells in the rheumatoid synovium, and IL-17-expressing cells in the peripheral blood, and synovial fluid were examined by confocal microscopy and flow cytometry, respectively. Peripheral blood neutrophils were cocultured either with rheumatoid arthritis synovial fibroblasts (RASF) or with conditioned medium from RASF that had been pre-exposed to recombinant human IL-17, TNFα or a combination of the two cytokines. Neutrophils were harvested and stained with the vital mitochondrial dye 3,3'-dihexyloxacarbocyanine iodide before being enumerated by flow cytometry. TH17-expressing CD4+ cells were found to accumulate within rheumatoid synovial tissue and in rheumatoid arthritis synovial fluid. RASF treated with IL-17 and TNFα (RASFIL-17/TNF) effectively doubled the functional lifespan of neutrophils in coculture. This was entirely due to soluble factors secreted from the fibroblasts. Specific depletion of granulocyte–macrophage colony-stimulating factor from RASFIL-17/TNF-conditioned medium demonstrated that this cytokine accounted for approximately one-half of the neutrophil survival activity. Inhibition of phosphatidylinositol-3-kinase and NF-κB pathways showed a requirement for both signalling pathways in RASFIL-17/TNF-mediated neutrophil rescue. The increased number of neutrophils with an extended lifespan found in the rheumatoid synovial microenvironment is partly accounted for by IL-17 and TNFα activation of synovial fibroblasts. TH17-expressing T cells within the rheumatoid synovium are likely to contribute significantly to this effect.
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DOI：
10.1084/jem.20061775
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sato K;Suematsu A;Okamoto K;Yamaguchi A;Morishita Y;Kadono Y;Tanaka S;Kodama T;Akira S;Iwakura Y;Cua DJ;Takayanagi H
通讯作者：
Takayanagi H
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
24.3
作者：
Laan, M;Prause, O;Lindén, A
通讯作者：
Lindén, A
影响因子：
4.4
作者：
Schwarzenberger, P;Huang, WT;Kolls, JK
通讯作者：
Kolls, JK
影响因子：
32.4
作者：
Veldhoen, M;Hocking, RJ;Stockinger, B
通讯作者：
Stockinger, B