Wang Lie, Wildt Kathryn F, Zhu Jinfang, Zhang Xianyu, Feigenbaum Lionel, Tessarollo Lino, Paul William E, Fowlkes B J, Bosselut Rémy
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Nat Immunol. 2008 Oct;9(10):1122-30. doi: 10.1038/ni.1647. Epub 2008 Sep 7.
The transcription factors GATA-3 and ThPOK are required for intrathymic differentiation of CD4(+) T cells, but their precise functions in this process remain unclear. Here we show that, contrary to previous findings, Gata3 disruption blocked differentiation into the CD4(+) T cell lineage before commitment to the CD4(+) lineage and in some contexts permitted the 'redirection' of major histocompatibility complex class II-restricted thymocytes into the CD8(+) lineage. GATA-3 promoted ThPOK expression and bound to a region of the locus encoding ThPOK established as being critical for ThPOK expression. Finally, ThPOK promoted differentiation into the CD4(+) lineage in a way dependent on GATA-3 but inhibited differentiation into the CD8(+) lineage independently of GATA-3. We propose that GATA-3 acts as a specification factor for the CD4(+) lineage 'upstream' of the ThPOK-controlled CD4(+) commitment checkpoint.
转录因子GATA-3和ThPOK是CD4(+) T细胞胸腺内分化所必需的，但它们在此过程中的精确功能仍不清楚。在这里我们表明，与之前的研究结果相反，Gata3基因破坏在定向分化为CD4(+)谱系之前就阻断了向CD4(+) T细胞谱系的分化，并且在某些情况下允许主要组织相容性复合体II类限制性胸腺细胞“重定向”为CD8(+)谱系。GATA-3促进ThPOK表达，并与已确定对ThPOK表达至关重要的ThPOK编码基因座区域结合。最后，ThPOK以依赖GATA-3的方式促进向CD4(+)谱系的分化，但独立于GATA-3抑制向CD8(+)谱系的分化。我们提出，GATA-3在ThPOK控制的CD4(+)定向检查点“上游”作为CD4(+)谱系的特异性因子发挥作用。
