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

Takuo Emoto, Jessie Lu, Tharini Sivasubramaniyam, Hassaan Maan, Aniqa B. Khan, Amina A. Abow, Stephanie A. Schroer, Sharon J. Hyduk, Marwan G. Althagafi, Trevor D. McKee, Fred Fu, Shiva Shabro, Antigona Ulndreaj, Felix Chiu, Elvira Paneda, Shaun Pacheco, Tao Wang, Angela Li, Jean X. Jiang, Peter LibbyMansoor Husain, Bo Wang, Barry B. Rubin, Myron I. Cybulsky, Clinton S. Robbins

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Macrophage colony stimulating factor-1 (CSF-1) plays a critical role in maintaining myeloid lineage cells. However, congenital global deficiency of CSF-1 (Csf1op/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.

Original languageEnglish (US)
Pages (from-to)862-878.e8
JournalImmunity
Volume55
Issue number5
DOIs
StatePublished - May 10 2022

Keywords

  • LEPR
  • LPS
  • Ly6Chigh monocytes
  • Ly6Cnegative monocytes
  • MCSF1
  • bone development
  • bone marrow niche
  • endothelial cell
  • hematopoeisis
  • lipopolysaccharide
  • macrophage
  • macrophage colony stimulating factor
  • mesenchymal stromal cell
  • monocyte
  • monopoiesis
  • osteoblast
  • osteocyte
  • osteopetrosis
  • perivascular niche
  • perivascular stromal cell
  • sepsis
  • sinusoid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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