Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Front Immunol. 2019 Jul 17;10:1642. doi: 10.3389/fimmu.2019.01642. eCollection 2019.
Classical and non-classical monocytes, and the macrophages and monocyte-derived dendritic cells they produce, play key roles in host defense against pathogens, immune regulation, tissue repair and many other processes throughout the body. Recent studies have revealed previously unappreciated heterogeneity among monocytes that may explain this functional diversity, but our understanding of mechanisms controlling the functional programming of distinct monocyte subsets remains incomplete. Resolving monocyte heterogeneity and understanding how their functional identity is determined holds great promise for therapeutic immune modulation. In this review, we examine how monocyte origins and developmental influences shape the phenotypic and functional characteristics of monocyte subsets during homeostasis and in the context of infection, inflammation, and cancer. We consider how extrinsic signals and transcriptional regulators impact monocyte production and functional programming, as well as the influence of epigenetic and metabolic mechanisms. We also examine the evidence that functionally distinct monocyte subsets are produced via different developmental pathways during homeostasis and that inflammatory stimuli differentially target progenitors during an emergency response. We highlight the need for a more comprehensive understanding of the relationship between monocyte ontogeny and heterogeneity, including multiparametric single-cell profiling and functional analyses. Studies defining mechanisms of monocyte subset production and maintenance of unique monocyte identities have the potential to facilitate the design of therapeutic interventions to target specific monocyte subsets in a variety of disease contexts, including infectious and inflammatory diseases, cancer, and aging.
经典单核细胞和非经典单核细胞，以及它们产生的巨噬细胞和单核细胞衍生的树突状细胞，在宿主防御病原体、免疫调节、组织修复和全身许多其他过程中发挥着关键作用。最近的研究揭示了单核细胞以前未被重视的异质性，这可能解释了这种功能多样性，但我们对控制不同单核细胞亚群功能编程的机制的理解仍不完整。解析单核细胞异质性并了解其功能特性如何确定，对于治疗性免疫调节具有巨大的潜力。在这篇综述中，我们研究了单核细胞的起源和发育影响如何在稳态和感染、炎症和癌症的背景下塑造单核细胞亚群的表型和功能特征。我们考虑了外在信号和转录调节剂如何影响单核细胞的产生和功能编程，以及表观遗传和代谢机制的影响。我们还研究了功能不同的单核细胞亚群是否通过稳态期间不同的发育途径产生，以及炎症刺激是否在应急反应中靶向不同的祖细胞的证据。我们强调需要更全面地了解单核细胞发生和异质性之间的关系，包括多参数单细胞分析和功能分析。研究确定单核细胞亚群产生和维持独特单核细胞特性的机制，有可能促进针对各种疾病背景（包括感染和炎症性疾病、癌症和衰老）中特定单核细胞亚群的治疗干预措施的设计。
