Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage
Open accessAbstract
M-CSF and GM-CSF are 2 important cytokines that regulate macrophage numbers and function. Here, we review their known effects on cells of the macrophage-monocyte lineage. Important clues to their function come from their expression patterns. M-CSF exhibits a mostly homeostatic expression pattern, whereas GM-CSF is a product of cells activated during inflammatory or pathologic conditions. Accordingly, M-CSF regulates the numbers of various tissue macrophage and monocyte populations without altering their “activation” status. Conversely, GM-CSF induces activation of monocytes/macrophages and also mediates differentiation to other states that participate in immune responses [i.e., dendritic cells (DCs)]. Further insights into their function have come from analyses of mice deficient in either cytokine. M-CSF signals through its receptor (CSF-1R). Interestingly, mice deficient in CSF-1R expression exhibit a more significant phenotype than mice deficient in M-CSF. This observation was explained by the discovery of a novel cytokine (IL-34) that represents a second ligand of CSF-1R. Information about the function of these ligands/receptor system is still developing, but its complexity is intriguing and strongly suggests that more interesting biology remains to be elucidated. Based on our current knowledge, several therapeutic molecules targeting either the M-CSF or the GM-CSF pathways have been developed and are currently being tested in clinical trials targeting either autoimmune diseases or cancer. It is intriguing to consider how evolution has directed these pathways to develop; their complexity likely mirrors the multiple functions in which cells of the monocyte/macrophage system are involved.
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GM-CSF and M-CSF are widely expressed in the vascular wall and regulate monocyte-to-macrophage differentiation as well as mature macrophage number and function.
“Two colony-stimulating factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), are widely expressed in the vascular wall149.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [150]
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Orecchioni, M., Ghosheh, Y., Pramod, A. B., & Ley, K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01084 · Cited by 2,063 · see citing works
Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities
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Development and Functions of Alveolar Macrophages
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New therapeutic avenues of MCSF for brain diseases and injuries
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- Authors
- Ushach, I., & Zlotnik, A.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Zlotnik, Albert
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-06-28
- Volume
- 100
- Issue
- 3
- Pages
- 481-489
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- PMC
- PMC4982611
- OpenAlex
- W2472029233
- Cited by
- 551
- References
- 153
- Citations by year
- 2026: 40 · 2025: 82 · 2024: 82 · 2023: 74 · 2022: 59 · 2021: 54 · 2020: 61 · 2019: 49 · 2018: 32 · 2017: 14 · 2016: 3 · 2013: 1
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- U.S. National Institutes of Health (R21AI117556)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- macrophage colony-stimulating factor, GM-CSF, myeloid lineage, macrophages, monocytes, CSF1R, IL-34, macrophage activation, dendritic cells, cytokine receptor signaling, autoimmune disease, cancer immunotherapy
- MeSH terms
- Animals, Humans, Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor, Cell Lineage, Myeloid Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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