Development and function of tissue resident macrophages in mice

Abstract

Macrophages are important for tissue development, homeostasis as well as immune response upon injury or infection. For a long time they were only seen as one uniform group of phagocytes with a common origin and similar functions. However, this view has been challenged in the last decade and revealed a complex diversity of tissue resident macrophages. Here, we want to present the current view on macrophage development and tissue specification and we will discuss differences as well as common patterns between heterogeneous macrophage subpopulations.

Keywords: Erythro-myeloid progenitor; Macrophage; Mononuclear phagocytes; Pulse labeling models; Tissue specification.

Figure 1. Embryonic development of resident tissue macrophages from erythromyeloid-progenitors in the yolk sac

The first progenitors of tissue resident macrophages arise from Tie2⁺ hemogenic/endothelial progenitors in the blood islands of the yolk sac (YS) as early as 7.5 days post coitum (dpc). These Tie2⁺ progenitors give rise to Myb-independent erythromyeloid progenitors (EMP), which are first detectable around 8.5 dpc in the YS and characterized by the expression of Csf1r. The EMP migrates to the embryo proper and gives rise to resident tissue macrophages, which are seeding embryonic tissues from 9.5 dpc onwards. These EMP-derived tissue macrophages actively proliferate within their developing tissues. Beside the EMP-derived tissue macrophages, there is another wave of myeloid cells developing after Myb-dependent hematopoietic stem cells (HSCs) emerge in the embryo starting at 10.5 dpc in the AGM (aorta-gonado-mesonephro) region, and their myeloid progeny can be detected between 10.5 and 14.5 dpc. In contrast to the proliferating self-renewing tissue macrophages, these cells are renewed by differentiation from proliferating HSCs in the fetal liver.