Transcriptional control of dendritic cell differentiation.
Transcriptional control of dendritic cell differentiation.
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DOI：
10.1007/82_2014_378
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发表时间：
2014
影响因子：
--
通讯作者：
I. Sasaki;T. Kaisho
中科院分区：
文献类型：
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作者：
I. Sasaki;T. Kaisho
树突状细胞(DC)是一种专职的抗原提呈细胞，不仅在激发先天免疫应答中发挥重要作用，而且在建立获得性免疫应答中也发挥着重要作用。树突状细胞是异质性的，分为几个亚群，包括浆类树突状细胞(PDC)和几种类型的常规树突状细胞(CDCs)，它们具有亚群特有的功能。类浆细胞树突状细胞的特点是能够产生大量的I型干扰素(IFN)，以响应核酸传感器TLR7和TLR9，并参与抗病毒免疫和某些自身免疫性疾病的发病机制，如牛皮癣。传统的DC包括具有高交叉压力活性的DC亚群，有助于抗病毒和抗肿瘤免疫。这些亚群是由造血干细胞(HSCs)通过几个中间前体细胞产生的，其发育受到转录机制的调控，其中亚群特异性转录因子起主要作用。我们最近发现，ETS家族转录因子SPI-B在pDC中大量表达，在pDC的功能和后期发育中起着关键作用。SPI-B与其他转录因子，特别是干扰素调节因子(IRF)家族成员协同发挥作用。本文就转录因子在DC产生和功能中的分子机制作一综述，主要集中在SPI-B及其相关分子的作用。
Dendritic cells (DCs) are professional antigen presenting cells involved critically not only in provoking innate immune responses but also in establishing adaptive immune responses. Dendritic cells are heterogenous and divided into several subsets, including plasmactyoid DCs (pDCs) and several types of conventional DCs (cDCs), which show subset-specific functions. Plasmactyoid DCs are featured by their ability to produce large amounts of type I interferons (IFNs) in response to nucleic acid sensors, TLR7 and TLR9 and involved in anti-viral immunity and pathogenesis of certain autoimmune disorders such as psoriasis. Conventional DCs include the DC subsets with high crosspresentation activity, which contributes to anti-viral and anti-tumor immunity. These subsets are generated from hematopoietic stem cells (HSCs) via several intermediate progenitors and the development is regulated by the transcriptional mechanisms in which subset-specific transcription factors play major roles. We have recently found that an Ets family transcription factor, SPI-B, which is abundantly expressed in pDCs among DC subsets, plays critical roles in functions and late stage development of pDCs. SPI-B functions in cooperation with other transcription factors, especially, interferon regulatory factor (IRF) family members. Here we review the transcription factor-based molecular mechanisms for generation and functions of DCs, mainly by focusing on the roles of SPI-B and its relatives.