Defining murine monocyte differentiation into colonic and ileal macrophages.

Mor Gross-Vered,Dena Leshkowitz,Sébastien Trzebanski,Anat Shemer,Louise Chappell-Maor,Tomer-Meir Salame,Steffen Jung,Caterina Curato,Sigalit Boura-Halfon,Biana Bernshtein,Gil Stelzer,Eyal David

doi:10.7554/elife.49998

Abstract

Monocytes are circulating short-lived macrophage precursors that are recruited on demand from the blood to sites of inflammation and challenge. In steady state, classical monocytes give rise to vasculature-resident cells that patrol the luminal side of the endothelium. In addition, classical monocytes feed macrophage compartments of selected organs, including barrier tissues, such as the skin and intestine, as well as the heart. Monocyte differentiation under conditions of inflammation has been studied in considerable detail. In contrast, monocyte differentiation under non-inflammatory conditions remains less well understood. Here we took advantage of a combination of cell ablation and precursor engraftment to investigate the generation of gut macrophages from monocytes. Collectively, we identify factors associated with the gradual adaptation of monocytes to tissue residency. Moreover, comparison of monocyte differentiation into the colon and ileum-resident macrophages revealed the graduated acquisition of gut segment-specific gene expression signatures.

Highlights

The recent past has seen major advance in our understanding of the diverse origins of tissue macrophages, as well as their discrete maintenance strategies
yolk sac (YS)-macrophage-derived macrophages persist throughout adulthood, while in most other tissues these cells are replaced by fetal monocytes that derive from multi-potent erythro-myeloid progenitors (EMP)
For the cell ablation we used [CD11c-DTR > WT] bone marrow (BM) chimeras, in which diphtheria toxin (DTx) receptor (DTR) transgenic intestinal macrophages can be conditionally ablated by DTx injection (Varol et al, 2007; Varol et al, 2009) (Figure 1A)

Summary

Introduction

The recent past has seen major advance in our understanding of the diverse origins of tissue macrophages, as well as their discrete maintenance strategies. Macrophages were shown to arise from three distinct developmental pathways that differentially contribute to the tissue compartments in the embryo and adult (Ginhoux and Guilliams, 2016). Embryonic tissue macrophages first develop from primitive macrophage progenitors that originate in the yolk sac (YS). YS-macrophage-derived macrophages persist throughout adulthood, while in most other tissues these cells are replaced by fetal monocytes that derive from multi-potent erythro-myeloid progenitors (EMP). Most EMP-derived tissue macrophage compartments persevere throughout adulthood without major input from HSC-derived cells; in certain barrier tissues, as well as selected other organs, like the heart, embryonic macrophages are progressively replaced by HSC-derived cells involving a blood monocyte intermediate (Varol et al, 2015)

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Conclusion