Department of Medical Sciences and Human Oncology, Dermatology Section, Turin University, Turin, Italy.
Dermatology. 2011;223(1):57-67. doi: 10.1159/000330330. Epub 2011 Aug 25.
Psoriasis is sustained by pro-inflammatory CD4+ T helper cells mainly belonging to the Th1, Th17 and Th22 lineage.
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.
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.
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.
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.
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。
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。
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。
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。
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。