GATA3参与蛋白激酶Cθ诱导的Th2细胞因子表达。

Involvement of GATA3 in protein kinase C theta-induced Th2 cytokine expression.

作者信息

Stevens Lisa, Htut Tin M, White Della, Li Xiang, Hanidu Adedayo, Stearns Carol, Labadia Mark E, Li Jun, Brown Maryanne, Yang Jianfei

机构信息

Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT 06877, USA.

出版信息

Eur J Immunol. 2006 Dec;36(12):3305-14. doi: 10.1002/eji.200636400.

DOI:10.1002/eji.200636400

PMID:17111354

Abstract

Protein kinase C theta (PKCtheta) is essential for T cell activation, as it is required for the activation of NF-kappaB and expression of IL-2. PKCtheta has also been shown to affect NFAT activation and Th2 differentiation. To better understand the role of PKCtheta in the regulation of T helper cells, we used PKCtheta-deficient DO11.10 transgenic T cells to study its role in vitro. DO11.10 Th1 cells deficient in PKCtheta produced significantly less TNF-alpha and IL-2. The expression of Th2 cytokines, including IL-4, IL-5, IL-10, IL-13 and IL-24 was significantly reduced in PKCtheta-deficient T cells. Moreover, the expression of the Th2 transcription factor, GATA3, was significantly reduced in PKCtheta-deficient T cells. Overexpression of GATA3 by retroviral infection in PKCtheta-deficient T cells resulted in increased expansion of IL-4-producing T cells and higher IL-4 production than that of wild type Th2 cells. IL-5, IL-10, IL-13 and IL-24 expressions were also rescued by GATA3 overexpression. Our observations suggest that PKCtheta regulates Th2 cytokine expression via GATA3.

摘要

蛋白激酶Cθ（PKCθ）对T细胞活化至关重要，因为它是激活核因子κB（NF-κB）和白细胞介素-2（IL-2）表达所必需的。PKCθ也已被证明会影响活化T细胞核因子（NFAT）的激活以及辅助性T细胞2（Th2）分化。为了更好地理解PKCθ在辅助性T细胞调节中的作用，我们使用缺乏PKCθ的DO11.10转基因T细胞在体外研究其作用。缺乏PKCθ的DO11.10 Th1细胞产生的肿瘤坏死因子-α（TNF-α）和IL-2显著减少。在缺乏PKCθ的T细胞中，包括IL-4、IL-5、IL-10、IL-13和IL-24在内的Th2细胞因子的表达显著降低。此外，在缺乏PKCθ的T细胞中，Th2转录因子GATA3的表达显著降低。通过逆转录病毒感染在缺乏PKCθ的T细胞中过表达GATA3，导致产生IL-4的T细胞扩增增加，且IL-4产量高于野生型Th2细胞。GATA3过表达也挽救了IL-5、IL-10、IL-13和IL-24的表达。我们的观察结果表明，PKCθ通过GATA3调节Th2细胞因子的表达。