Colony-stimulating factors in inflammation and autoimmunity
Abstract
Although they were originally defined as haematopoietic-cell growth factors, colony-stimulating factors (CSFs) have been shown to have additional functions by acting directly on mature myeloid cells. Recent data from animal models indicate that the depletion of CSFs has therapeutic benefit in many inflammatory and/or autoimmune conditions and as a result, early-phase clinical trials targeting granulocyte/macrophage colony-stimulating factor and macrophage colony-stimulating factor have now commenced. The distinct biological features of CSFs offer opportunities for specific targeting, but with some associated risks. Here, I describe these biological features, discuss the probable specific outcomes of targeting CSFs in vivo and highlight outstanding questions that need to be addressed.
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CSF-1R signaling is critical for microglial development.
“CSF-1R-mediated signaling is critical for microglial development.”
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CSF-2 promotes migration of blood-borne monocytes across the blood-brain barrier, which then differentiate into macrophages in the presence of CSF-1 and CSF-2.
“CSF-2 promotes migration of blood-borne monocytes across the blood-brain barrier, which then differentiate into macrophages in the presence of CSF-1 and CSF-2 [16, 17, 26, 52].”
From Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy (2020) · cites this paper as [17]
CSF-2 in isolation also promotes differentiation of monocytes into a dendritic cell lineage, which maintains a phagocytic phenotype (CD68 immunopositive).
“CSF-2 in isolation also promotes their differentiation into a dendritic cell lineage, which maintains a phagocytic phenotype (CD68 immunopositive) [17, 30].”
From Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy (2020) · cites this paper as [17]
Pulmonary GM-CSF treatment has some drawbacks such as inflammatory activity that can render its use in humans problematic by exacerbating inflammatory lung injury.
“Although pulmonary GM-CSF treatment has some drawbacks such as inflammatory activity (43) that can render its use in humans problematic by exacerbating inflammatory lung injury, the results of our study are promising.”
From Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections (2013) · cites this paper as [43]
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- Authors
- Hamilton, J. A.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Hamilton, John A.
- ORCID
- Hamilton, John A.
- Venue
- Nature reviews. Immunology
- Published
- 2008-07
- Volume
- 8
- Issue
- 7
- Pages
- 533-544
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2063680739
- Cited by
- 1,305
- References
- 141
- Citations by year
- 2026: 33 · 2025: 45 · 2024: 49 · 2023: 57 · 2022: 81 · 2021: 83 · 2020: 75 · 2019: 63 · 2018: 82 · 2017: 94 · 2016: 85 · 2015: 92 · 2014: 94 · 2013: 71 · 2012: 89
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- colony-stimulating factors, inflammation, autoimmunity, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, myeloid cells, hematopoietic growth factors
- MeSH terms
- Animals, Arthritis, Colony-Stimulating Factors, Encephalomyelitis, Autoimmune, Experimental, Humans, Inflammation, Lung Diseases, Neoplasms, Nephritis, Autoimmunity, Receptors, Colony-Stimulating Factor, Atherosclerosis
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