Monocyte, Macrophage, and Dendritic Cell Development: the Human Perspective

The maintenance of monocytes, macrophages, and dendritic cells (DCs) involves manifold pathways of ontogeny and homeostasis that have been the subject of intense study in recent years. The concept of a peripheral mononuclear phagocyte system continually renewed by blood-borne monocytes has been modified to include specialized DC pathways of development that do not involve monocytes, and longevity through self-renewal of tissue macrophages. The study of development remains difficult owing to the plasticity of phenotypes and misconceptions about the fundamental structure of hematopoiesis. However, greater clarity has been achieved in distinguishing inflammatory monocyte-derived DCs from DCs arising in the steady state, and new concepts of conjoined lymphomyeloid hematopoiesis more easily accommodate the shared lymphoid and myeloid phenotypes of some DCs. Cross-species comparisons have also yielded coherent systems of nomenclature for all mammalian monocytes, macrophages, and DCs. Finally, the clear relationships between ontogeny and functional specialization offer information about the regulation of immune responses and provide new tools for the therapeutic manipulation of myeloid mononuclear cells in medicine.