Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis.
Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis.
复制标题
DOI：
10.1186/s13075-015-0688-0
复制
发表时间：
2015-07-09
影响因子：
4.9
通讯作者：
Baeten DL
中科院分区：
文献类型：
--
作者：
Cañete JD;Celis R;Yeremenko N;Sanmartí R;van Duivenvoorde L;Ramírez J;Blijdorp I;García-Herrero CM;Pablos JL;Baeten DL
滑膜异位淋巴新生（ELN）在类风湿性关节炎（RA）中的功能相关性仍然未知。由于ELN与组织炎症程度相关，我们研究了ELN是否与特定的细胞因子谱相关。通过免疫组织学和长CD 21亚型（CD 21 L）表达测定滑膜ELN。通过多重酶联免疫吸附试验（ELISA）和定量聚合酶链反应（PCR）以及免疫组织学分别测定滑膜液（SF）（n = 44）和组织（ST）（n = 108）中的细胞因子表达。体外研究了成纤维细胞样滑膜细胞（FLS）产生ELN相关趋化因子的情况。通过多重ELISA对SF的筛选分析显示，ELN+样品中的白细胞介素（IL）-23（p = 0.018）和IL-17 F（p = 0.028）的蛋白水平高于ELN-样品。其他细胞因子，包括IL-17 A、IL-6和肿瘤坏死因子（TNF）-α，无差异。IL-23和ELN之间的相关性不受疾病活动或其他临床特征的影响，并且通过ELN+与ELN-ST样本中更高的IL-23 mRNA表达得到证实。（p = 0.030），相同样本中IL-23和CD 21 L表达之间的相关性（r = 0.70 p < 0.0001），并且在两个独立的ST样本组中具有类似的相关性（r = 0.778 p < 0.0001和r = 0.817 p = 0.011）。IL-23 p19染色在异位淋巴滤泡附近既不受限制也不增强，IL-23和IL-17 A刺激均不诱导FLS表达ELN相关CC趋化因子配体CCL 21和CXC趋化因子配体CXCL 13。在两个独立的ST样本集中，IL-23下游，CD 21 L表达与IL-17 F、IL-21和IL-22显著相关，但与IL-17 A无关。RA中的滑膜ELN与IL-23通路的激活密切相关，但与IL-17 A无关。本文的在线版本（doi：10.1186/s13075-015-0688-0）包含补充材料，可供授权用户使用。
The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively. Production of ELN-associated chemokines by fibroblast-like synoviocytes (FLS) was studied in vitro. Screening analysis of SF by multiplex ELISA showed higher protein levels of interleukin (IL)-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples. Other cytokines, including IL-17A, IL-6, and tumor necrosis factor (TNF)-α, were not different. The association between IL-23 and ELN was not biased by disease activity or other clinical features and was confirmed by higher IL-23 mRNA expression in ELN+ versus ELN- ST samples (p = 0.030), a correlation between IL-23 and CD21L expression in the same samples (r = 0.70 p < 0.0001), and a similar correlation in two independent ST sample sets (r = 0.778 p < 0.0001 and r = 0.817 p = 0.011). IL-23 p19 staining was neither restricted nor enhanced in close proximity of ectopic lymphoid follicles, and neither IL-23 nor IL-17A stimulation induced expression of the ELN-associated CC chemokine ligand, CCL21 and CXC chemokine ligand CXCL13, by FLS. Downstream of IL-23, CD21L expression was significantly associated with IL-17F, IL-21, and IL-22, but not IL-17A in two independent ST sample sets. Synovial ELN in RA is strongly associated with activation of the IL-23 pathway but not with IL-17A. The online version of this article (doi:10.1186/s13075-015-0688-0) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.9
作者：
Celis R;Planell N;Fernández-Sueiro JL;Sanmartí R;Ramírez J;González-Álvaro I;Pablos JL;Cañete JD
通讯作者：
Cañete JD
异位LT Alphaββ指导淋巴器官新生成，并具有外周节点地址和HEV限制的磺胺转移酶的表达。
DOI：
10.1084/jem.20021761
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Drayton DL;Ying X;Lee J;Lesslauer W;Ruddle NH
通讯作者：
Ruddle NH
影响因子：
27.4
作者：
Brentano, F.;Ospelt, C.;Kyburz, D.
通讯作者：
Kyburz, D.
影响因子：
3.7
作者：
Del Rey MJ;Faré R;Izquierdo E;Usategui A;Rodríguez-Fernández JL;Suárez-Fueyo A;Cañete JD;Pablos JL
通讯作者：
Pablos JL
影响因子：
3.7
作者：
Moran EM;Heydrich R;Ng CT;Saber TP;McCormick J;Sieper J;Appel H;Fearon U;Veale DJ
通讯作者：
Veale DJ