Embryo-derived tissue-resident macrophages are the first representatives of the haematopoietic lineage to emerge in metazoans. In mammals, resident macrophages originate from early yolk sac progenitors and are specified into tissue-specific subsets during organogenesis—establishing stable spatial and functional relationships with specialized tissue cells—and persist in adults. Resident macrophages are an integral part of tissues together with specialized cells: for instance, microglia reside with neurons in brain, osteoclasts reside with osteoblasts in bone, and fat-associated macrophages reside with white adipocytes in adipose tissue. This ancillary cell type, which is developmentally and functionally distinct from haematopoietic stem cell and monocyte-derived macrophages, senses and integrates local and systemic information to provide specialized tissue cells with the growth factors, nutrient recycling and waste removal that are critical for tissue growth, homeostasis and repair. Resident macrophages contribute to organogenesis, promote tissue regeneration following damage and contribute to tissue metabolism and defence against infectious disease. A correlate is that genetic or environment-driven resident macrophage dysfunction is a cause of degenerative, metabolic and possibly inflammatory and tumoural diseases. In this Review, we aim to provide a conceptual outline of our current understanding of macrophage physiology and its importance in human diseases, which may inform and serve the design of future studies.

胚胎来源的组织驻留巨噬细胞是后生动物中出现的造血谱系的第一个代表。在哺乳动物中，常驻巨噬细胞起源于早期卵黄囊祖细胞，并在器官发生过程中被指定为组织特异性亚群，与专门的组织细胞建立稳定的空间和功能关系，并在成年体内持续存在。常驻巨噬细胞与特殊细胞一起是组织的组成部分：例如，小胶质细胞与大脑中的神经元一起存在，破骨细胞与骨骼中的成骨细胞一起存在，与脂肪相关的巨噬细胞与脂肪组织中的白色脂肪细胞一起存在。这种辅助细胞类型在发育和功能上与造血干细胞和单核细胞衍生的巨噬细胞不同，它感知并整合局部和全身信息，为专门的组织细胞提供对组织生长至关重要的生长因子、营养回收和废物清除，体内平衡和修复。常驻巨噬细胞有助于器官发生，促进损伤后的组织再生，并有助于组织代谢和防御传染病。与之相关的是，遗传或环境驱动的常驻巨噬细胞功能障碍是退行性、代谢性疾病以及可能的炎症和肿瘤疾病的原因。在这篇综述中，我们的目标是提供我们目前对巨噬细胞生理学及其在人类疾病中的重要性的理解的概念性概述，这可能为未来的研究设计提供信息和服务。