Zhou Meixia, Ouyang Wenjun
Department of Pathology, Washington University School of Medicine, St. Louis, MO, USA.
Immunol Res. 2003;28(1):25-37. doi: 10.1385/IR:28:1:25.
GATA-3 plays a central role in regulating Th1 and Th2 cell differentiation. Upon interleukin (IL)-4 binding to its receptor, GATA-3 is induced through the action of Stat6. GATA-3 regulates Th2 cytokine expression not only at the transcription level, such as directly binding to the promoters of the IL-5 and IL-13 gene, but also by the involvement in the remodeling of the chromatin structure and opening the IL-4 locus. As a master control, GATA-3 stabilizes the Th2 phenotype by two methods. First, GATA-3 shuts down Th1 development through the repression the IL-12 receptor beta2-chain expression. Second, GATA-3 augments its own expression by a positive feedback autoregulation. In this article, we review the recent study of the function of GATA-3 in Th1 and Th2 differentiation.
GATA-3在调节Th1和Th2细胞分化过程中发挥核心作用。白细胞介素(IL)-4与其受体结合后,通过信号转导和转录激活因子6(Stat6)的作用诱导GATA-3表达。GATA-3不仅在转录水平调节Th2细胞因子的表达,例如直接结合白细胞介素-5(IL-5)和白细胞介素-13(IL-13)基因的启动子,还参与染色质结构重塑并打开IL-4基因座。作为主要调控因子,GATA-3通过两种方式稳定Th2细胞表型。第一,GATA-3通过抑制IL-12受体β2链的表达来阻断Th1细胞的发育。第二,GATA-3通过正反馈自动调节增强自身的表达。在本文中,我们综述了GATA-3在Th1和Th2细胞分化中功能的最新研究进展。