Macrophages: Biology and Role in the Pathology of Diseases

Macrophages: Biology and Role in the Pathology of Diseases
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巨噬细胞:生物学及其在疾病病理学中的作用

DOI:
10.1007/978-1-4939-1311-4_22
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发表时间:
2014
期刊:
--
影响因子:
--
通讯作者:
Eames H
Eames H
中科院分区:
--
文献类型:
--
作者:
Eames H

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干扰素调节因子(IRF)家族转录因子最初与抗病毒反应和I型干扰素(IFN)的产生有关。随后的研究揭示了它们在抗微生物反应和细胞分化调控中的多方面作用。特别是,IRF8现在被认为是调节骨髓细胞生长和分化的主要因子之一,而IRF5和IRF4分别与M1和M2巨噬细胞极化有关。此外,IRF因子似乎为NFκB调控的免疫基因表达赋予信号特异性提供了一种机制。例如,IRF3的上游激酶激活发生在脂多糖(LPS)刺激TLR4和双链RNA (dsRNA)刺激TLR3的反应中,而在许多其他诱导NFκB的信号通路中不被激活。IRF家族的另一个新特征是,该家族的不同成员似乎针对特定的基因亚群,其中IRF3对抗病毒I型IFN反应至关重要,而IRF5在诱导促炎细胞因子和趋化因子中起关键作用。本章将讨论IRF蛋白在巨噬细胞生物学中的多方面功能。
The interferon regulatory factor (IRF) family of transcription factors was originally implicated in anti-viral responses and Type I interferon (IFN) production. Subsequent studies revealed their multifaceted role in regulation of anti-microbial responses and cell differentiation. In particular, IRF8 is now known as one of the major factors regulating myeloid cell growth and differentiation, while IRF5 and IRF4 are associated with M1 and M2 macrophage polarisation, respectively. In addition, IRF factors appear to provide a mechanism for conferring signal specificity to expression of immune genes regulated by NFκB. For example, IRF3, whose activation by upstream kinases occurs in response to TLR4 stimulation by lipopolysaccharide (LPS) and TLR3 stimulation by double stranded RNA (dsRNA), is not activated in many other NFκB inducing signalling pathways. Another emerging feature of the IRF family is that different members of the family seem to target specific gene subsets, with IRF3 being essential for anti-viral Type I IFN responses, and IRF5 playing a key role in induction of pro-inflammatory cytokines and chemokines. This chapter will discuss the multifaceted functions of IRF proteins in macrophage biology.
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