Final Report Summary - MPS2010 (In vivo biology of the mononuclear phagocyte system. A molecular & functional approach)
Our project aimed at a global understanding of the biology of phagocytes, a family of cells involved in the defense against microbes, the removal of dead, dying and unfit cells from tissue, the growth, repair and remodeling of tissues under a steady state and inflammatory conditions. At the time of the award this phagocyte system was generally considered to consists in hematopoietic progenitors located in the bone marrow in adult mammals, circulating precursors or white blood cells called monocytes, and tissue macrophages originating from the blood monocytes.
The ERC funding has allowed us to obtain robust and genetic, molecular, and cellular experimental evidence leading to a complete redefinition of tissue macrophages. We demonstrated that the development of tissue macrophage is integral to organogenesis, identified of their main precursors (erythro-myeloid progenitors from the yolk sac, distinct from hematopoietic stem cells), the steps involved in the colonisation of the organ anlage, and the transcriptional programs involved in- and in some cases responsible for- their specification into liver macrophages (kupffer cells), brain macrophages (microglia), lung alveolar macrophages, epidermal Langerhans cells and kidney resident macrophages. It follows that resident macrophages can be distinguished from recruited leucocytes, and this allows the study of their specific functions in infection, tumor development, inflammation and degenerative diseases, and more generally in tissue growth repair and remodeling. We, and a number of other laboratories, have started these studies investigating in particular the in vivo functions of kidney resident macrophages.
The ERC funding has allowed us to obtain robust and genetic, molecular, and cellular experimental evidence leading to a complete redefinition of tissue macrophages. We demonstrated that the development of tissue macrophage is integral to organogenesis, identified of their main precursors (erythro-myeloid progenitors from the yolk sac, distinct from hematopoietic stem cells), the steps involved in the colonisation of the organ anlage, and the transcriptional programs involved in- and in some cases responsible for- their specification into liver macrophages (kupffer cells), brain macrophages (microglia), lung alveolar macrophages, epidermal Langerhans cells and kidney resident macrophages. It follows that resident macrophages can be distinguished from recruited leucocytes, and this allows the study of their specific functions in infection, tumor development, inflammation and degenerative diseases, and more generally in tissue growth repair and remodeling. We, and a number of other laboratories, have started these studies investigating in particular the in vivo functions of kidney resident macrophages.