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Colony stimulating factor-1 producing endothelial cells and mesenchymal stromal cells maintain monocytes within a

Takuo Emoto1, Jessie Lu2, Tharini Sivasubramaniyam3

  • 1Toronto General Research Institute, University Health Network, Toronto, ON, Canada; Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Immunity
|May 4, 2022
PubMed

Insights

Macrophage colony-stimulating factor-1 (CSF-1) from bone marrow cells supports monocyte development. Endothelial cells and mesenchymal stromal cells provide CSF-1, crucial for monocyte survival and function, especially during sepsis.

Area of Science:

  • Immunology
  • Hematology
  • Cell Biology

Background:

  • Macrophage colony-stimulating factor-1 (CSF-1) is vital for myeloid cell maintenance.
  • Congenital CSF-1 deficiency (Csf1op/op) leads to musculoskeletal defects impacting hematopoiesis.
  • Osteolineage-derived CSF-1 prevents developmental abnormalities but not adult monopoiesis.

Purpose of the Study:

  • To investigate the role of CSF-1 in adult monopoiesis and monocyte function.
  • To identify the cellular sources of CSF-1 within the bone marrow niche.
  • To determine the impact of CSF-1 on monocyte behavior during sepsis.

Main Methods:

  • Conditional deletion of Csf1 in adult mice.
  • Bone histology and cellular localization studies.
  • Sepsis induction and monitoring of monocyte populations and weight loss.

Main Results:

  • Ubiquitous adult Csf1 deletion reduced monocyte survival, differentiation, and migration.
  • Monocytes were found near sinusoidal endothelial cells (ECs) and leptin receptor (Lepr)-expressing mesenchymal stromal cells (MSCs).
  • Targeted Csf1 deletion from ECs reduced Ly6C- monocytes; combined deletion from ECs and MSCs further reduced Ly6Chi cells.
  • EC-derived CSF-1 aided Ly6C- monocyte recovery and protected against sepsis-induced weight loss.

Conclusions:

  • Distinct cellular sources of CSF-1 within the perivascular bone marrow niche support monocytes.
  • Endothelial cells and MSCs are key sources of CSF-1 regulating monocyte populations.
  • EC-derived CSF-1 is critical for monocyte recovery during inflammatory conditions like sepsis.

Keywords:
LEPRLPSLy6Chigh monocytesLy6Cnegative monocytesMCSF1bone developmentbone marrow nicheendothelial cellhematopoeisislipopolysaccharidemacrophagemacrophage colony stimulating factormesenchymal stromal cellmonocytemonopoiesisosteoblastosteocyteosteopetrosisperivascular nicheperivascular stromal cellsepsissinusoid

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