Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses.

Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses.
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通过TNF抑制来改善表皮增生与TH17反应减少有关。

DOI:
10.1084/jem.20071094
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发表时间:
2007-12-24
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Krueger JG
Krueger JG
中科院分区:
其他
文献类型:
--
作者:
Zaba LC;Cardinale I;Gilleaudeau P;Sullivan-Whalen M;Suárez-Fariñas M;Fuentes-Duculan J;Novitskaya I;Khatcherian A;Bluth MJ;Lowes MA;Krueger JG

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生物制剂极大地改善了严重牛皮癣患者的治疗选择。依那西普(肿瘤坏死因子 [TNF] 受体-免疫球蛋白融合蛋白)是许多银屑病患者的有效治疗方法,阻断 TNF 被认为是其主要作用。然而,在这项临床试验中,我们证明依那西普对一种新认识的 T 细胞类型:辅助性 T 细胞 17 (Th17) 细胞具有早期抑制作用。依那西普减少了驱动 Th17 细胞增殖的炎症树突状细胞产物(白细胞介素 [IL] 23),以及 Th17 细胞产物和下游效应分子(IL-17、IL-22、CC 趋化因子配体 20 和 β-防御素 4)。相比之下,Th1 细胞产物和效应分子(干扰素 γ、淋巴毒素 α 和粘病毒抗性 1)在疾病消退后期减少。这项研究表明,除 Th1 细胞外,Th17 细胞在银屑病的发病机制中也发挥着作用。 Th17 细胞在驱动银屑病斑块的表皮激活方面可能特别重要,而 Th1 细胞也必须被消除才能最终解决疾病。
Biological agents have dramatically improved treatment options for patients with severe psoriasis. Etanercept (tumor necrosis factor [TNF] receptor–immunoglobulin fusion protein) is an effective treatment for many psoriasis patients, and blockade of TNF is considered to be its primary action. However, in this clinical trial, we show that etanercept has early inhibitory effects on a newly appreciated type of T cells: T helper type 17 (Th17) cells. Etanercept reduced the inflammatory dendritic cell products that drive Th17 cell proliferation (interleukin [IL] 23), as well as Th17 cell products and downstream effector molecules (IL-17, IL-22, CC chemokine ligand 20, and β-defensin 4). In contrast, Th1 cellular products and effector molecules (interferon γ, lymphotoxin α, and myxovirus resistance 1) were reduced late in disease resolution. This study suggests a role for Th17 in addition to Th1 cells in the pathogenesis of psoriasis. Th17 cells may be particularly important in driving epidermal activation in psoriatic plaques, whereas Th1 cells must also be eliminated for final disease resolution.
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