Department of Pulmonary Medicine, Erasmus MC, 3000 CA Rotterdam, the Netherlands.
Innate Immunity Unit, Institut Pasteur, 75724 Paris, France; INSERM U668, 75724 Paris, France.
Immunity. 2014 Aug 21;41(2):191-206. doi: 10.1016/j.immuni.2014.06.006.
The zinc-finger transcription factor GATA-3 has received much attention as a master regulator of T helper 2 (Th2) cell differentiation, during which it controls interleukin-4 (IL-4), IL-5, and IL-13 expression. More recently, GATA-3 was shown to contribute to type 2 immunity through regulation of group 2 innate lymphoid cell (ILC2) development and function. Furthermore, during thymopoiesis, GATA-3 represses B cell potential in early T cell precursors, activates TCR signaling in pre-T cells, and promotes the CD4(+) T cell lineage after positive selection. GATA-3 also functions outside the thymus in hematopoietic stem cells, regulatory T cells, CD8(+) T cells, thymic natural killer cells, and ILC precursors. Here we discuss the varied functions of GATA-3 in innate and adaptive immune cells, with emphasis on its activity in T cells and ILCs, and examine the mechanistic basis for the dose-dependent, developmental-stage- and cell-lineage-specific activity of this transcription factor.
锌指转录因子 GATA-3 作为 T 辅助细胞 2(Th2)细胞分化的主要调节因子受到广泛关注,在此过程中它控制白细胞介素 4(IL-4)、IL-5 和 IL-13 的表达。最近,GATA-3 通过调节 2 型固有淋巴细胞(ILC2)的发育和功能,被证明有助于 2 型免疫。此外,在胸腺发生过程中,GATA-3 在早期 T 细胞前体中抑制 B 细胞潜能,在 pre-T 细胞中激活 TCR 信号,并在阳性选择后促进 CD4(+)T 细胞谱系。GATA-3 在造血干细胞、调节性 T 细胞、CD8(+)T 细胞、胸腺自然杀伤细胞和 ILC 前体细胞中也在胸腺外发挥作用。在这里,我们讨论了 GATA-3 在先天和适应性免疫细胞中的多种功能,重点介绍了它在 T 细胞和 ILC 中的活性,并研究了这种转录因子在剂量依赖性、发育阶段特异性和细胞谱系特异性活性的机制基础。