Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and β-catenin
Open accessAbstract
Macrophage colony-stimulating factor (M-CSF) influences the proliferation and survival of mononuclear phagocytes through the receptor CSF-1R. The adaptor protein DAP12 is critical for the function of mononuclear phagocytes. DAP12-mutant mice and humans have defects in osteoclasts and microglia, as well as brain and bone abnormalities. Here we show DAP12 deficiency impaired the M-CSF-induced proliferation and survival of macrophages in vitro. DAP12-deficient mice had fewer microglia in defined central nervous system areas, and DAP12-deficient progenitors regenerated myeloid cells inefficiently after bone marrow transplantation. Signaling by M-CSF through CSF-1R induced the stabilization and nuclear translocation of beta-catenin, which activated genes involved in the cell cycle. DAP12 was essential for phosphorylation and nuclear accumulation of beta-catenin. Our results provide a mechanistic explanation for the many defects of DAP12-deficient mononuclear phagocytes.
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TREM2 promotes proliferation, survival, and phagocytosis of apoptotic cells.
“TREM2 promotes proliferation (119), survival (119), and phagocytosis of apoptotic cells (120–122).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [119]
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References 50 · Cited by 315
Research works printed but not linked: 1
- [10]Roussel MF Regulation of cell cycle entry and G1 progression by CSF-1 Mol Reprod Dev 1997 46 11 8 8981358
- Authors
- Otero, K., Turnbull, I. R., Poliani, P. L., Vermi, W., Cerutti, E., Aoshi, T., Tassi, I., Takai, T., Stanley, S. L., Miller, M., Shaw, A. S., & Colonna, M.
- Affiliations
- Washington University in St. Louis (US)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- Tohoku University (JP)
- Corresponding author
- Colonna, Marco
- ORCID
- Venue
- Nature Immunology
- Published
- 2009-06-07
- Volume
- 10
- Issue
- 7
- Pages
- 734-743
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4004764
- OpenAlex
- W2085663788
- Cited by
- 315
- References
- 50
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 20 · 2023: 35 · 2022: 23 · 2021: 23 · 2020: 21 · 2019: 13 · 2018: 18 · 2017: 16 · 2016: 18 · 2015: 24 · 2014: 20 · 2013: 15 · 2012: 15
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM077279)
- National Institute of Allergy and Infectious Diseases (U54 AI1057160, U54AI057160)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- macrophage colony-stimulating factor, DAP12, β-catenin, CSF1R, macrophage proliferation, macrophage survival, mononuclear phagocytes, microglia, osteoclasts, β-catenin nuclear translocation, cell cycle genes
- MeSH terms
- Animals, Brain, Calcium-Binding Proteins, Cell Adhesion, Cell Cycle, Cell Survival, Cells, Cultured, Flow Cytometry, Immunohistochemistry, Macrophages, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Transgenic, Microfilament Proteins, Phosphorylation, Immunoblotting, Signal Transduction, Macrophage Colony-Stimulating Factor, Mice, Knockout, Adaptor Proteins, Signal Transducing, Cell Proliferation, Green Fluorescent Proteins, beta Catenin, Mice, Focal Adhesion Kinase 2
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