Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, USA.
Trends Immunol. 2013 May;34(5):216-23. doi: 10.1016/j.it.2012.11.001. Epub 2012 Dec 4.
Macrophage polarization refers to development of a specific phenotype important for tissue homeostasis or host defense in response to environmental cues. Environmental factors that induce macrophage polarization include cytokines and microbial factors produced by pathogens or commensal microbiota. Signaling pathways utilized by these polarizing factors have been well characterized, but it is less clear how signals are converted into complex and sustained patterns of gene expression, and how macrophages are reprogrammed during polarization to alter their responses to subsequent environmental challenges. Emerging evidence, reviewed here, suggests an important role for epigenetic mechanisms in modulating and transmitting signals during macrophage polarization and reprogramming. Deeper understanding of epigenetic regulation of macrophage phenotype will enable development of gene-specific therapeutic approaches to enhance host defense while preserving tissue integrity and preventing chronic inflammatory diseases.
巨噬细胞极化是指巨噬细胞为了应对环境信号，朝着有利于组织内稳态或宿主防御的特定表型发展。诱导巨噬细胞极化的环境因素包括细胞因子和病原体或共生菌群产生的微生物因子。这些极化因子所利用的信号通路已得到很好的描述，但信号如何转化为复杂和持续的基因表达模式，以及巨噬细胞在极化过程中如何被重新编程以改变它们对随后环境挑战的反应，这些问题还不太清楚。本文回顾了新兴证据，这些证据表明表观遗传机制在巨噬细胞极化和重编程过程中信号的调节和传递中发挥着重要作用。深入了解巨噬细胞表型的表观遗传调控将能够开发针对特定基因的治疗方法，以增强宿主防御能力，同时保持组织完整性，预防慢性炎症性疾病。
