Independent production of distinct monocyte subsets by granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs)

Abstract

Abstract Myeloid cells – neutrophils, monocytes and dendritic cells (DCs) – play key roles in inflammation, immune defense against pathogens, and tissue repair and remodeling. Myelopoiesis, the production of myeloid cells by hematopoietic stem and progenitor cells, must be carefully regulated to support immune surveillance in the steady-state and meet the additional demands of emergency conditions such as infections. The current widely-accepted model of myelopoiesis describes the production of neutrophils by granulocyte-monocyte progenitors (GMPs), which also yield monocytes and DCs via monocyte-DC progenitors (MDPs). However, our data show that murine GMPs do not give rise to MDPs and that conventional and plasmacytoid DCs (cDCs and pDCs) are produced by MDPs but not GMPs. Thus GMPs and MDPs arise separately but both yield monocytes. Our in vitro and in vivo studies of the pathways and mechanisms of monocyte production have revealed that both GMPs and MDPs yield Ly6C+ inflammatory monocytes and Ly6C− CD43+ monocytes, but that GMP-derived and MDP-derived Ly6C+ inflammatory monocytes exhibit distinct patterns of gene expression. In ongoing studies we are comparing the phenotype and function of GMP- and MDP-derived monocytes, and determining the relative contributions of GMPs and MDPs to the monocyte and tissue macrophage pools under steady-state and emergency conditions.