The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Immunol Rev. 2010 Nov;238(1):63-75. doi: 10.1111/j.1600-065X.2010.00955.x.
The ETS family transcription factor PU.1 is one of the best-studied regulators of hematopoiesis. While research over the past two decades has established that PU.1 is essential for many aspects of lymphoid and myeloid cell development, the more recent development of the tools that enable PU.1 function to be assessed in adult mice and in specific cell lineages has led to the discovery of some surprising new roles of this versatile factor in the adaptive immune response. Despite being required for fetal lymphopoiesis, PU.1 is dispensable for the differentiation of committed B cells. There is, however, an emerging and still uncharacterized function of PU.1 as a repressor for late B-cell differentiation. In contrast, PU.1 is required at every point for the differentiation of all dendritic cells, in part, although its regulation of the crucial receptor Flt3. Within the T-cell lineage, PU.1 is required for the earliest thymic development, although the mechanism remains unknown, while recent studies have shown a previously unknown function of PU.1 in peripheral T-cell differentiation. Here, we review insights derived from these mouse models of PU.1 deficiency, with particular emphasis on these functions of PU.1 in the lymphocyte and dendritic cell lineages.
ETS 家族转录因子 PU.1 是研究最为深入的造血调控因子之一。尽管过去二十年的研究已经确立了 PU.1 对于淋巴样和髓样细胞发育的许多方面都是必不可少的，但最近开发的工具使得能够在成年小鼠和特定细胞谱系中评估 PU.1 的功能，这导致了人们发现这个多功能因子在适应性免疫反应中有一些令人惊讶的新作用。尽管 PU.1 对于胎儿淋巴样发生是必需的，但它对于定向 B 细胞的分化是可有可无的。然而，PU.1 作为晚期 B 细胞分化的抑制剂的作用正在浮现，并且尚未得到充分描述。相比之下，PU.1 在分化为所有树突状细胞的过程中都是必需的，部分原因是它调节关键受体 Flt3。在 T 细胞谱系中，PU.1 对于最早的胸腺发育是必需的，尽管其机制仍然未知，而最近的研究表明 PU.1 在周围 T 细胞分化中有一个以前未知的功能。在这里，我们综述了这些缺乏 PU.1 的小鼠模型所带来的见解，特别强调了 PU.1 在淋巴细胞和树突状细胞谱系中的这些作用。
