Biology of resident tissue macrophages.

Although best known for their phagocytic and immunological functions, macrophages have increasingly been recognised as key players in the development, homeostasis and regeneration of their host tissues. Early during development, macrophages infiltrate and colonise all tissues within the body, developing symbiotically with their host tissues and acquiring unique functional adaptations based on the tissue microenvironment. These embryonic resident tissue macrophages (RTMs) are ontogenically distinct from the later adult bone marrow-derived monocytes, and in some tissues are self-maintained independently of general circulation at a steady state. In this article, we briefly discuss the ontogeny, maintenance and unique tissue adaptions of RTMs focusing on microglia, Kupffer cells, Langerhans cells, intestinal macrophages, cardiac macrophages and tumour-associated macrophages, and highlight their role in development, homeostasis and dysfunction.

Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.