Colony stimulating factor-1 producing endothelial cells and mesenchymal stromal cells maintain monocytes within a perivascular bone marrow niche.

Macrophage colony stimulating factor-1 (CSF-1) plays a critical role in maintaining myeloid lineage cells. However, congenital global deficiency of CSF-1 (Csf1 op/op ) causes severe musculoskeletal defects that may indirectly affect hematopoiesis. Indeed, we show here that osteolineage-derived Csf1 prevented developmental abnormalities but had no effect on monopoiesis in adulthood. However, ubiquitous deletion of Csf1 conditionally in adulthood decreased monocyte survival, differentiation, and migration, independent of its effects on bone development. Bone histology revealed that monocytes reside near sinusoidal endothelial cells (ECs) and leptin receptor (Lepr)-expressing perivascular mesenchymal stromal cells (MSCs). Targeted deletion of Csf1 from sinusoidal ECs selectively reduced Ly6C− monocytes, whereas combined depletion of Csf1 from ECs and MSCs further decreased Ly6Chi cells. Moreover, EC-derived CSF-1 facilitated recovery of Ly6C− monocytes and protected mice from weight loss following induction of polymicrobial sepsis. Thus, monocytes are supported by distinct cellular sources of CSF-1 within a perivascular BM niche. • CSF-1 maintains monocytes within a bone marrow perivascular niche • Osteolineage-derived CSF-1 prevents bone defects but is not required for monopoiesis • CSF-1-producing ECs and Lepr+ perivascular MSCs support Ly6Chi and Ly6C− monocytes • CSF-1 ensures reestablishment of monocyte homeostasis following polymicrobial sepsis CSF-1 is an important maintenance factor for monocytes, but the functionally important CSF-1 producing bone marrow niche cells are unknown. Emoto et al. reveal that Ly6C− monocytes are maintained by CSF-1 producing sinusoidal endothelial cells, whereas Ly6Chi monocytes require combined production of CSF-1 by endothelium and Lepr+ perivascular stromal cells. [ABSTRACT FROM AUTHOR]