Introduction: Special Issue—The Origins of Macrophages and Their Roles Beyond Immunology

In the context of ontogeny and phylogeny, macrophages emerge much earlier than other hematopoietic cells, including monocytes, implying that their roles extend beyond immunology. Phagocytosis, a representative function of macrophages, has been examined since the late 19th century and such studies were the basis of characterizing innate immunity. Macrophages also make a range of cytokines important in both innate and adaptive immunity. Recently, their non-immunological homeostatic roles in organ development, angiogenesis, tissue repair/regeneration and metabolism have also become clear. This involvement in so many responses in virtually all tissues requires them to be enormously flexible but their phenotypic and functional heterogeneity have made it difficult to delineate the origins of macrophages in specific sites under different circumstances.