Macrophage Development Rewritten Macrophages provide protection against a wide variety of infections and critically shape the inflammatory environment in many tissues. These cells come in many flavors, as determined by differences in gene expression, cell surface phenotype and specific function. Schulz et al. (p. 86, published online 22 March) investigated whether adult macrophages all share a common developmental origin. Immune cells, including most macrophages, are widely thought to arise from hematopoietic stem cells (HSCs), which require the transcription factor Myb for their development. Analysis of Myb-deficient mice revealed that a population of yolk-sac–derived, tissue-resident macrophages was able to develop and persist in adult mice in the absence of HSCs. Importantly, yolk sac–derived macrophages also contributed substantially to the tissue macrophage pool even when HSCs were present. In mice, a population of tissue-resident macrophages arises independently of bone marrow–derived stem cells. Macrophages and dendritic cells (DCs) are key components of cellular immunity and are thought to originate and renew from hematopoietic stem cells (HSCs). However, some macrophages develop in the embryo before the appearance of definitive HSCs. We thus reinvestigated macrophage development. We found that the transcription factor Myb was required for development of HSCs and all CD11bhigh monocytes and macrophages, but was dispensable for yolk sac (YS) macrophages and for the development of YS-derived F4/80bright macrophages in several tissues, such as liver Kupffer cells, epidermal Langerhans cells, and microglia—cell populations that all can persist in adult mice independently of HSCs. These results define a lineage of tissue macrophages that derive from the YS and are genetically distinct from HSC progeny.

A lineage of myeloid cells independent of Myb and hematopoietic stem cells

Monocytes and macrophages have crucial and distinct roles in tissue homeostasis and immunity, but they also contribute to a broad spectrum of pathologies and are thus attractive therapeutic targets. Potential intervention strategies that aim to manipulate these cells will require an in-depth understanding of their origins and the mechanisms that ensure their homeostasis. Recent evidence shows that monocytes do not substantially contribute to most tissue macrophage populations in the steady state or during certain types of inflammation. Rather, most tissue macrophage populations in mice are derived from embryonic precursors, are seeded before birth and can maintain themselves in adults by self-renewal. In this Review, we discuss the evidence that has dramatically changed our understanding of monocyte and macrophage development, and the maintenance of these cells in the steady state.

Monocytes and macrophages: developmental pathways and tissue homeostasis

Luca Melchiori

Papers

Lymphomyeloid Contribution of an Immune-Restricted Progenitor Emerging Prior to Definitive Hematopoietic Stem Cells

Dicer is selectively important for the earliest stages of erythroid development