Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Immunol Rev. 2010 Nov;238(1):110-25. doi: 10.1111/j.1600-065X.2010.00954.x.
GATA family transcription factors play multiple vital roles in hematopoiesis in many cell lineages, and in particular, T cells require GATA-3 for execution of several developmental steps. Transcriptional activation of the Gata3 gene is observed throughout T-cell development and differentiation in a stage-specific fashion. GATA-3 has been described as a master regulator of T-helper 2 (Th2) cell differentiation in mature CD4(+) T cells. During T-cell development in the thymus, its roles in the CD4 versus CD8 lineage choice and at the β-selection checkpoint are the best characterized. In contrast, its importance prior to β-selection has been obscured both by the developmental heterogeneity of double negative (DN) 1 thymocytes and the paucity of early T-lineage progenitors (ETPs), a subpopulation of DN1 cells that contains the most immature thymic progenitors that retain potent T-lineage developmental potential. By examining multiple lines of in vivo evidence procured through the analysis of Gata3 mutant mice, we have recently demonstrated that GATA-3 is additionally required at the earliest stage of thymopoiesis for the development of the ETP population. Here, we review the characterized functions of GATA-3 at each stage of T-cell development and discuss hypothetical molecular pathways that mediate these functions.
GATA 家族转录因子在许多细胞谱系的造血中发挥着多种重要作用，特别是 T 细胞需要 GATA-3 来执行几个发育步骤。Gata3 基因的转录激活在 T 细胞发育和分化的整个过程中以特定的阶段特异性方式发生。GATA-3 被描述为成熟 CD4(+) T 细胞中 T 辅助 2 (Th2)细胞分化的主调控因子。在胸腺中的 T 细胞发育过程中，其在 CD4 与 CD8 谱系选择以及β选择检查点的作用得到了最好的描述。相比之下，其在β选择之前的重要性由于双阴性 (DN) 1 胸腺细胞的发育异质性和早期 T 谱系祖细胞 (ETP) 的缺乏而变得模糊不清，ETP 是 DN1 细胞的一个亚群，其中包含最不成熟的胸腺祖细胞，保留着强大的 T 谱系发育潜能。通过分析 Gata3 突变小鼠获得的多种体内证据，我们最近证明，GATA-3 在胸腺发生的最早阶段对于 ETP 群体的发育也是必需的。在这里，我们回顾了 GATA-3 在 T 细胞发育的每个阶段的特征性功能，并讨论了介导这些功能的假设分子途径。
