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寻常型银屑病患者外周血单个核细胞及皮损中 Th1 和 Th2 细胞相关转录因子 T-bet、GATA-3 的表达。

Expression of Th1 and Th2 cytokine-associated transcription factors, T-bet and GATA-3, in peripheral blood mononuclear cells and skin lesions of patients with psoriasis vulgaris.

机构信息

Department of Dermatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

出版信息

Arch Dermatol Res. 2010 Sep;302(7):517-23. doi: 10.1007/s00403-010-1048-1. Epub 2010 Mar 24.

Abstract

Psoriasis is considered as a T cell-mediated autoimmune disease, and the Th1 response has been established as the major immune agent in its pathomechanisms. The relative expression of Th1 and Th2 transcription factors, T-bet and GATA-3, resulting in a swing in the Th1/Th2 pendulum, has been implicated in a number of immunological diseases. However, their expression and correlation with psoriasis has not yet been studied. Our aim was to evaluate the expression of T-bet and GATA-3 in psoriatic patients and determine their correlation with serum levels of IFN-gamma and IL-4. Sera, peripheral blood mononuclear cells (PBMCs) and skin lesions were taken from 23 patients with psoriasis vulgaris. Serum levels of IFN-gamma and IL-4 were measured by ELISA. T-bet and GATA-3 mRNA expression in PBMCs was analyzed by RT-PCR. Lesional expression and distribution of CD4, CD8, T-bet and GATA-3 were assessed by immunohistochemistry. Blood and skin samples of healthy individuals served as controls. A markedly higher IFN-gamma and lower IL-4 concentration in the serum of psoriatic patients was found. A significantly higher expression of T-bet mRNA and a lower expression of GATA-3 mRNA in PBMCs, and consequently, a much higher T-bet/GATA-3 ratio in patients than in controls were shown. T-bet mRNA expression was strongly correlated with serum IFN-gamma secretion in patients; furthermore, the correlation between T-bet/GATA-3 ratio and IFN-gamma/IL-4 ratio was revealed. We also observed a significant increase in CD4+ cells and T-bet positive cells in psoriatic lesions. These results suggested that T-bet and GATA-3 might be regulator genes for psoriasis via the Th1/Th2 balance, and the Th1-specific transcription factor, T-bet, may play an important role in the development and maintenance of psoriasis.

摘要

银屑病被认为是一种 T 细胞介导的自身免疫性疾病,Th1 反应已被确立为其发病机制中的主要免疫因子。Th1 和 Th2 转录因子 T-bet 和 GATA-3 的相对表达导致 Th1/Th2 摆动的摆动,与许多免疫性疾病有关。然而,它们在银屑病中的表达及其相关性尚未得到研究。我们的目的是评估银屑病患者中 T-bet 和 GATA-3 的表达,并确定它们与血清 IFN-γ和 IL-4 水平的相关性。从 23 例寻常型银屑病患者中采集血清、外周血单个核细胞(PBMC)和皮肤病变。通过 ELISA 测量血清 IFN-γ和 IL-4 水平。通过 RT-PCR 分析 PBMC 中 T-bet 和 GATA-3 mRNA 的表达。通过免疫组化评估 CD4、CD8、T-bet 和 GATA-3 在皮肤病变中的表达和分布。健康个体的血液和皮肤样本作为对照。发现银屑病患者血清中 IFN-γ明显升高,IL-4 浓度降低。PBMC 中 T-bet mRNA 表达显著升高,GATA-3 mRNA 表达降低,因此患者 T-bet/GATA-3 比值明显高于对照组。T-bet mRNA 表达与患者血清 IFN-γ分泌强烈相关;此外,还揭示了 T-bet/GATA-3 比值与 IFN-γ/IL-4 比值之间的相关性。我们还观察到银屑病皮损中 CD4+细胞和 T-bet 阳性细胞显著增加。这些结果表明,T-bet 和 GATA-3 可能通过 Th1/Th2 平衡成为银屑病的调节基因,Th1 特异性转录因子 T-bet 可能在银屑病的发生和维持中发挥重要作用。

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