Cited by 551Immune cells in cancerCytokine Signaling Pathways and InteractionsPhagocytosis and Immune Regulation

Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage

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Ushach, Irina, Zlotnik, Albert·2016·Journal of Leukocyte Biology

Abstract

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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Crossref · 10.1189/jlb.3ru0316-144r

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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.”

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Authors
Ushach, I., & Zlotnik, A.
Affiliations
University of California, Irvine (US)
Corresponding author
Zlotnik, Albert
Venue
Journal of Leukocyte Biology
Published
2016-06-28
Volume
100
Issue
3
Pages
481-489
ISSN
  • 0741-5400 (ISSN-L)
  • 1938-3673
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
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

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