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银屑病患者的 Th1、Th2、Th17 和调节性 T 细胞模式:依那西普治疗诱导的细胞因子和基因靶点的调节及其与临床反应的相关性。

Th1, Th2, Th17 and regulatory T cell pattern in psoriatic patients: modulation of cytokines and gene targets induced by etanercept treatment and correlation with clinical response.

机构信息

Department of Medical Sciences and Human Oncology, Dermatology Section, Turin University, Turin, Italy.

出版信息

Dermatology. 2011;223(1):57-67. doi: 10.1159/000330330. Epub 2011 Aug 25.

Abstract

BACKGROUND

Psoriasis is sustained by pro-inflammatory CD4+ T helper cells mainly belonging to the Th1, Th17 and Th22 lineage.

OBJECTIVE

To identify whether treatment with the anti-tumour-necrosis-factor antagonist etanercept is able to induce significant modulations in transcription factor and cytokine mRNA gene expressions related to the different T cell immune response polarization (Th1, Th2, Th17 and regulatory T cells, Treg and to correlate them with clinical response.

METHODS

The study population included 19 psoriasis patients treated with etanercept and 19 healthy subjects. Blood samples were collected at baseline and every 4 weeks during treatment. Taqman quantitative real-time polymerase chain reaction was applied to analyse the expression of: Stat-4, T-bet, IL-12p35 and IFN-γ (Th1-related); GATA-3, IL-4 (Th2-related); Stat-3, RORγt, IL-23p19 (Th17-related); Foxp3, IL-2 (Treg-related). Flow cytometry was applied to analyse CD4+CD25+(bright)Foxp3+ cells in peripheral blood.

RESULTS

Upregulation of Th1 and Th17 and downregulation of Treg subsets was found at baseline. The response to etanercept could be associated with a significant reversal of the Th1/Th17 activation, and a concomitant upregulation of Th2 and Treg subsets.

CONCLUSION

Our data may contribute to a better understanding of the mechanisms underlying the achievement of clinical response in psoriasis and could be helpful for the identification of early predictive markers of response.

摘要

背景

银屑病由主要属于 Th1、Th17 和 Th22 谱系的促炎 CD4+T 辅助细胞持续存在。

目的

确定抗肿瘤坏死因子拮抗剂依那西普治疗是否能够诱导与不同 T 细胞免疫反应极化(Th1、Th2、Th17 和调节性 T 细胞、Treg)相关的转录因子和细胞因子 mRNA 基因表达的显著调节,并将其与临床反应相关联。

方法

研究人群包括 19 名接受依那西普治疗的银屑病患者和 19 名健康对照者。在基线和治疗期间每 4 周采集血样。应用 Taqman 定量实时聚合酶链反应分析以下基因的表达:Stat-4、T-bet、IL-12p35 和 IFN-γ(与 Th1 相关);GATA-3、IL-4(与 Th2 相关);Stat-3、RORγt、IL-23p19(与 Th17 相关);Foxp3、IL-2(与 Treg 相关)。应用流式细胞术分析外周血中 CD4+CD25+(bright)Foxp3+细胞。

结果

在基线时发现 Th1 和 Th17 的上调和 Treg 亚群的下调。依那西普的反应可能与 Th1/Th17 激活的显著逆转以及 Th2 和 Treg 亚群的同时上调相关。

结论

我们的数据可能有助于更好地理解银屑病临床反应的发生机制,并有助于识别反应的早期预测标志物。

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