MAcrophages are found in all tissues and were originially identified by the Nobel Prize winner Ilya Metchnikoff (1845-1916) as cells specialized in the phagocytosis and killing of microorganisms. Based on the MOnonuclear Phagocyte System (MPS) concept from Ralph van Furth (1969), it was long believed that macrophages differentiate continuously from circulating monocytes. However, our knowledge of the biology of tissue-resident macrophages is currently undergoing a genuine conceptual revolution. (1) We now appreciate that macrophages do not only act as sentinels against infiltrating pathogens but also regulate hematopoiesis, vascularization, tissue-repair and metabolism. (2) Genetic profiling of macrophages from various tissues has demonstrated the astonishing diversity of these cells, suggesting that each macrophage is profoundly adapted to its tissue of residence and performs unique local homeostatic functions. (3) It is now becoming clear that most tissue-resident macrophages do not derive from circulating adult precursors but develop before birth from embryonic precursors and then self-maintain throughout life. I would like to understand how these cells adapt themselves to their tissue of residence and to what purpose they do so. I therefore want to generate novel tools that will enable me to identify what daily function these cells perform in these organs in which they self-maintain seemingly indefinitely and what molecular mechanisms underlie these function.