Regulation of myelopoiesis by the transcription factor IRF8
Regulation of myelopoiesis by the transcription factor IRF8
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DOI：
10.1007/s12185-015-1761-9
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发表时间：
2015-04-01
影响因子：
2.1
通讯作者：
Koizumi, Shin-ichi
中科院分区：
文献类型：
--
作者：
Tamura, Tomohiko;Kurotaki, Daisuke;Koizumi, Shin-ichi
干扰素调节因子-8（IRF 8）是在造血细胞中表达的转录因子，特别是在单核吞噬细胞[单核细胞/巨噬细胞和树突状细胞（DC）]及其祖细胞中。各种研究已经证明IRF 8对于单核细胞、DC、嗜酸性粒细胞和嗜碱性粒细胞的发育是必需的。相反，IRF 8抑制中性粒细胞的产生。因此，Irf 8（-/-）小鼠发展免疫缺陷和慢性髓性白血病（CML）样疾病。人IRF 8基因的突变和表达丧失也分别与免疫缺陷和CML相关。最近的研究结果已经开始揭示由IRF 8控制的转录因子网络和表观遗传变化。例如，在单核吞噬细胞祖细胞中，IRF 8与PU. 1合作促进启动子远端增强子的形成，以诱导单核细胞相关基因，包括关键下游转录因子基因Klf 4。另一方面，IRF 8阻断C/EBP α活性以抑制中性粒细胞分化程序。事实上，Irf 8（-/-）单核吞噬细胞祖细胞不能有效地产生单核细胞和DC，而是异常地产生嗜中性粒细胞。本文就IRF 8在骨髓细胞生成及相关疾病中的作用作一综述。
Interferon regulatory factor-8 (IRF8) is a transcription factor expressed in hematopoietic cells, particularly in mononuclear phagocytes [monocytes/macrophages and dendritic cells (DCs)] and their progenitors. Various studies have demonstrated that IRF8 is essential for the development of monocytes, DCs, eosinophils, and basophils. Conversely, IRF8 suppresses the generation of neutrophils. Accordingly, Irf8 (-/-) mice develop immunodeficiency and a chronic myeloid leukemia (CML)-like disease. Mutations and loss of expression of the human IRF8 gene are also associated with immunodeficiency and CML, respectively. Recent findings have begun to reveal the transcription factor network and epigenetic changes governed by IRF8. For example, in mononuclear phagocyte progenitors, IRF8 cooperates with PU.1 to promote the formation of promoter-distal enhancers to induce monocyte-related genes including the critical downstream transcription factor gene Klf4. On the other hand, IRF8 blocks C/EBP alpha activity to suppress the neutrophil differentiation program. Indeed, Irf8 (-/-) mononuclear phagocyte progenitors fail to efficiently generate monocytes and DCs and, instead, aberrantly give rise to neutrophils. This article provides an overview of recent advances in our understanding of the role of IRF8 in myelopoiesis and related diseases.