Inhibition of TNFα during maturation of dendritic cells results in the development of semi-mature cells: a potential mechanism for the beneficial effects of TNFα blockade in rheumatoid arthritis
Inhibition of TNFα during maturation of dendritic cells results in the development of semi-mature cells: a potential mechanism for the beneficial effects of TNFα blockade in rheumatoid arthritis
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树突状细胞成熟过程中 TNFα 的抑制导致半成熟细胞的发育：TNFα 阻断对类风湿性关节炎有益作用的潜在机制
DOI：
10.1136/ard.2004.023259
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发表时间：
2004
影响因子：
27.4
通讯作者：
T. Radstake
中科院分区：
文献类型：
--
作者：
A. V. Lieshout;P. Barrera;R. Smeets;G. Pesman;P. Riel;W. B. V. D. Berg;T. Radstake
背景：树突状细胞通过产生细胞因子和趋化因子来协调关键的免疫过程。目的：评估树突状细胞成熟过程中肿瘤坏死因子α（TNFα）的中和是否影响其表型和行为，这可能解释TNFα中和在类风湿关节炎中的有益作用。研究方法：未成熟和完全成熟的树突状细胞培养从血液单核细胞类风湿性关节炎患者和健康对照以下标准化的协议。通过加入p55可溶性TNFα受体PEGsTNFRI中和TNFα。通过流式细胞术研究TNFα中和对树突状细胞表型（CD14、CD16、CD32、CD64、CD80、CD83、CD86和MHC）的影响。检测树突状细胞分化和成熟过程中趋化因子（CCL17、CCL18、CCL19、CCL22、CCL3和CXCL8）的表达以及IL 1 β和IL 6的产生。结果如下：在类风湿患者或健康对照组中，在树突状细胞分化和成熟过程中TNFα的中和并没有导致树突状细胞表型的改变。相反，在脂多糖触发的树突状细胞成熟过程中，当TNFα活性受到抑制时，树突状细胞的CCL17、CCL18、CCL19、CCL22、CCL3和CXCL8的表达显著降低。PEGsTNFRI可抑制成熟树突状细胞产生IL 1 β和IL 6。结论：在树突状细胞成熟过程中抑制TNFα活性可导致半成熟细胞的发育。这些数据表明，TNFα的中和可能通过一种新的途径发挥其治疗作用。
Background: Dendritic cells orchestrate pivotal immunological processes mediated by the production of cytokines and chemokines. Objective: To assess whether neutralisation of tumour necrosis factor α (TNFα) during maturation of dendritic cells affects their phenotype and behaviour, which might explain the beneficial effects of TNFα neutralisation in rheumatoid arthritis. Methods: Immature and fully matured dendritic cells were cultured from blood monocytes from patients with rheumatoid arthritis and healthy controls following standardised protocols. TNFα was neutralised by addition of the p55 soluble TNFα receptor, PEGsTNFRI. The effect of TNFα neutralisation on the phenotype (CD14, CD16, CD32, CD64, CD80, CD83, CD86, and MHC) of dendritic cells was investigated by flow cytometry. Expression of chemokines (CCL17, CCL18, CCL19, CCL22, CCL3, and CXCL8) and production of IL1β and IL6 during dendritic cell differentiation and maturation were examined. Results: Neutralisation of TNFα during the differentiation and maturation of dendritic cells did not result in an altered dendritic cell phenotype in the rheumatoid patients or the healthy controls. In contrast, the expression of CCL17, CCL18, CCL19, CCL22, CCL3, and CXCL8 by dendritic cells was significantly reduced when TNFα activity was inhibited during lipopolysaccharide triggered dendritic cell maturation. The production of IL1β and IL6 by mature dendritic cells was inhibited by PEGsTNFRI. Conclusions: Inhibition of TNFα activity during dendritic cell maturation leads to the development of semi-mature cells. These data suggest a novel pathway by which the neutralisation of TNFα might exert its therapeutic effects.
影响因子：
--
作者：
Smeets, RL;van de Loo, FAJ;van den Berg, WB
通讯作者：
van den Berg, WB
影响因子：
--
作者：
Halla,JT;Koopman,WJ;Fallahi,S;Oh,SJ;Gay,RE;Schrohenloher,RE
通讯作者：
Schrohenloher,RE
影响因子：
15.9
作者：
Morita, Y;Yang, JM;Fox, DA
通讯作者：
Fox, DA