Macrophage biology in development, homeostasis and disease

A discussion of progress in macrophage biology, examining their classification, diverse lineages, identities and regulation, their roles in regulating normal physiology and development, and their identification as therapeutic targets in human diseases. Macrophages are phagocytic cells found in blood, lymph and in all mammalian tissue types. They have many and diverse roles in normal development, homeostasis, tissue repair and the immune response to pathogens. Their diversity means that they are involved in almost every human disease and are prime therapeutic targets because their function can be augmented or inhibited to alter disease outcome. A Review in this issue discusses macrophage physiology in terms of the homeostatic mechanisms by which macrophages contribute to physiological and pathophysiologic adaptations in mammals. Macrophages, the most plastic cells of the haematopoietic system, are found in all tissues and show great functional diversity. They have roles in development, homeostasis, tissue repair and immunity. Although tissue macrophages are anatomically distinct from one another, and have different transcriptional profiles and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this Review, we discuss how macrophages regulate normal physiology and development, and provide several examples of their pathophysiological roles in disease. We define the ‘hallmarks’ of macrophages according to the states that they adopt during the performance of their various roles, taking into account new insights into the diversity of their lineages, identities and regulation. It is essential to understand this diversity because macrophages have emerged as important therapeutic targets in many human diseases.