Homeostasis in the mononuclear phagocyte system

•CSF1R signaling controls monocyte–macrophage homeostasis.•Macrophage replenishment from monocytes versus self-renewal varies between adult tissues.•Tissue macrophages derive from monocytes at some point in development.•The MPS concept remains valid but may exclude classical DCs.

The mononuclear phagocyte system (MPS) is a family of functionally related cells including bone marrow precursors, blood monocytes, and tissue macrophages. We review the evidence that macrophages and dendritic cells (DCs) are separate lineages and functional entities, and examine whether the traditional view that monocytes are the immediate precursors of tissue macrophages needs to be refined based upon evidence that macrophages can extensively self-renew and can be seeded from yolk sac/foetal liver progenitors with little input from monocytes thereafter. We review the role of the growth factor colony-stimulating factor (CSF)1, and present a model consistent with the concept of the MPS in which local proliferation and monocyte recruitment are connected to ensure macrophages occupy their well-defined niche in most tissues.