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 Libby; Mansoor Husain; Bo Wang; Barry B Rubin; Myron I Cybulsky; Clinton S Robbins

doi:10.1016/j.immuni.2022.04.005

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

Immunity. 2022 May 10;55(5):862-878.e8. doi: 10.1016/j.immuni.2022.04.005. Epub 2022 May 3.

Authors

Takuo Emoto¹, Jessie Lu², Tharini Sivasubramaniyam³, Hassaan Maan⁴, Aniqa B Khan⁵, Amina A Abow², Stephanie A Schroer³, Sharon J Hyduk³, Marwan G Althagafi², Trevor D McKee⁶, Fred Fu⁶, Shiva Shabro⁶, Antigona Ulndreaj³, Felix Chiu², Elvira Paneda³, Shaun Pacheco³, Tao Wang⁷, Angela Li⁵, Jean X Jiang⁸, Peter Libby⁹, Mansoor Husain¹⁰, Bo Wang¹¹, Barry B Rubin¹², Myron I Cybulsky¹³, Clinton S Robbins¹⁴

Affiliations

¹ Toronto 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.
² Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
³ Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
⁴ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Vector Institute for Artificial Intelligence, Toronto, ON, Canada.
⁵ Department of Immunology, University of Toronto, Toronto, ON, Canada.
⁶ STTARR Innovation Centre, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
⁷ Department of Physiology, University of Toronto, Toronto, ON, Canada.
⁸ Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁹ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁰ Toronto General Research Institute, University Health Network, Toronto, ON, Canada; Ted Rogers Centre for Heart Research, Toronto, ON, Canada; Peter Munk Cardiac Centre, Toronto, ON, Canada.
¹¹ Vector Institute for Artificial Intelligence, Toronto, ON, Canada; Peter Munk Cardiac Centre, Toronto, ON, Canada.
¹² Peter Munk Cardiac Centre, Toronto, ON, Canada.
¹³ Toronto General Research Institute, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Peter Munk Cardiac Centre, Toronto, ON, Canada.
¹⁴ Toronto General Research Institute, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Peter Munk Cardiac Centre, Toronto, ON, Canada. Electronic address: clint.robbins@utoronto.ca.

PMID: 35508166
DOI: 10.1016/j.immuni.2022.04.005

Abstract

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 Ly6C^hi 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.

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.

MeSH terms

Animals
Bone Marrow
Bone Marrow Cells
Endothelial Cells
Macrophage Colony-Stimulating Factor* / pharmacology
Mesenchymal Stem Cells*
Mice
Monocytes

Substances

Macrophage Colony-Stimulating Factor