Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and Ets factor Spi-B
Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and Ets factor Spi-B
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DOI：
10.1002/eji.200838470
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发表时间：
2008-09-01
影响因子：
5.4
通讯作者：
Blom, Bianca
中科院分区：
文献类型：
--
作者：
Nagasawa, Maho;Schmidlin, Heike;Blom, Bianca
浆细胞样树突状细胞（pDC）是针对病毒感染的先天性和适应性免疫应答中的核心参与者。从祖细胞发育pDC的分子机制才刚刚开始阐明。先前，我们报道了Ets因子Spi-B和DNA结合蛋白2（Id 2）或Id 3的抑制剂，其拮抗E蛋白活性，分别关键地参与促进或损害pDC发育。在这里，我们表明，基本的螺旋-环-螺旋蛋白E2-2主要在pDC中表达，而不是在其祖细胞或传统的DC。在祖细胞中强制表达E2-2刺激pDC发育。相反，通过RNA干扰抑制E2-2表达损害了pDC的产生，表明E2-2在这些细胞的发育中起关键作用。值得注意的是，Spi-B不能克服pDC发育中的Id 2强制阻断，而且Spi-B转导的pDC表达降低的Id 2水平。这可能表明Spi-B通过促进E2-2活性而有助于pDC发育。与概念一致，祖细胞中E2-2和Spi-B的同时过表达进一步刺激pDC发育。总之，我们的研究结果提供了额外的洞察转录网络控制pDC的发展所证明的E2-2和Spi-B的合资企业。
Plasmacytoid dendritic cells (pDC) are central players in the innate and adaptive immune response against viral infections. The molecular mechanism that underlies pDC development from progenitor cells is only beginning to be elucidated. Previously, we reported that the Ets factor Spi-B and the inhibitors of DNA binding protein 2 (Id2) or Id3, which antagonize E-protein activity, are crucially involved in promoting or impairing pDC development, respectively. Here we show that the basic helix-loop-helix protein E2-2 is predominantly expressed in pDC, but not in their progenitor cells or conventional DC. Forced expression of E2-2 in progenitor cells stimulated pDC development. Conversely, inhibition of E2-2 expression by RNA interference impaired the generation of pDC suggesting a key role of E2-2 in development of these cells. Notably, Spi-B was unable to overcome the Id2 enforced block in pDC development and moreover Spi-B transduced pDC expressed reduced Id2 levels. This might indicate that Spi-B contributes to pDC development by promoting E2-2 activity. Consistent with notion, simultaneous overexpression of E2-2 and Spi-B in progenitor cells further stimulated pDC development. Together our results provide additional insight into the transcriptional network controlling pDC development as evidenced by the joint venture of E2-2 and Spi-B.