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Macrophage polarization: the epigenetic point of view

机译：巨噬细胞极化：表观遗传学观点

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Purpose of review:The first functions of macrophages to be identified by Metchnikoff were phagocytosis and microbial killing. Although these are important features, macrophages are functionally very complex and involved in virtually all aspects of life, from immunity and host defense, to homeostasis, tissue repair and development. To accommodate for this, macrophages adopt a plethora of polarization states. Understanding their transcriptional regulation and phenotypic heterogeneity is vital because macrophages are critical in many diseases and have emerged as attractive targets for therapy. Here, we review how epigenetic mechanisms control macrophage polarization.Recent findings:It is becoming increasingly clear that chromatin remodelling governs multiple aspects of macrophage differentiation, activation and polarization. In recent years, independent research groups highlighted the importance of epigenetic mechanisms to regulate enhancer activity. Moreover, distinct histone-modifying enzymes were identified that control macrophage activation and polarization.Summary:We recap epigenetic features of distinct enhancers and describe the role of Jumonji domain-containing protein 3 (Jmjd3) and Hdac3 as crucial mediators of macrophage differentiation, activation and polarization. We hypothesize that epigenetic enzymes could serve as the link between environment, cellular metabolism and macrophage phenotype. To conclude, we propose epigenetic intervention as a future pharmacological target to modulate macrophage polarization and to treat inflammatory diseases such as atherosclerosis.
机译：综述目的：通过Metchnikoff鉴定的巨噬细胞的第一个功能是吞噬作用和杀灭微生物。尽管这些是重要的特征，但是巨噬细胞在功能上非常复杂，并且实际上涉及生活的各个方面，从免疫和宿主防御到体内平衡，组织修复和发育。为了适应这一点，巨噬细胞采用了过多的极化态。了解巨噬细胞的转录调控和表型异质性至关重要，因为巨噬细胞在许多疾病中都至关重要，并且已经成为治疗的诱人靶标。在这里，我们回顾了表观遗传机制如何控制巨噬细胞极化。最近发现：染色质重塑支配着巨噬细胞分化，激活和极化的多个方面，这一点变得越来越清楚。近年来，独立的研究小组强调了表观遗传机制调节增强子活性的重要性。此外，我们还确定了可控制巨噬细胞活化和极化的独特组蛋白修饰酶。极化。我们假设表观遗传酶可以作为环境，细胞代谢和巨噬细胞表型之间的联系。总而言之，我们提出表观遗传学干预作为未来的药理学目标，以调节巨噬细胞极化和治疗炎性疾病，如动脉粥样硬化。

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