A novel strategy to dissect multifaceted macrophage function in human diseases
Open accessAbstract
Macrophages are widely distributed immune cells that play central roles in a variety of physiologic and pathologic processes, including obesity and cardiovascular disease (CVD). They are highly plastic cells that execute diverse functions according to a combination of signaling and environmental cues. While macrophages have traditionally been understood to polarize to either proinflammatory M1-like or anti-inflammatory M2-like states, evidence has shown that they exist in a spectrum of states between those 2 phenotypic extremes. In obesity-related disease, M1-like macrophages exacerbate inflammation and promote insulin resistance, while M2-like macrophages reduce inflammation, promoting insulin sensitivity. However, polarization markers are expressed inconsistently in adipose tissue macrophages, and they additionally exhibit phenotypes differing from the M1/M2 paradigm. In atherosclerotic CVD, activated plaque macrophages can also exist in a range of proinflammatory or anti-inflammatory states. Some of these macrophages scavenge lipids, developing into heterogeneous foam cell populations. To better characterize the many actions of macrophages in human disease, we have designed a novel set of computational tools: MacSpectrum and AtheroSpectrum. These tools provide information on the inflammatory polarization status, differentiation, and foaming of macrophages in both human and mouse samples, allowing for better characterization of macrophage subpopulations based on their function. Using these tools, we identified disease-relevant cell states in obesity and CVD, including the novel concept that macrophage-derived foam cell formation can follow homeostatic noninflammatory or pathogenic inflammatory foaming programs.
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Macrophages exist along a continuum of activation states, with M1 and M2 representing the prototypical pro- and anti-inflammatory extremes.
“Although macrophages have traditionally been classified as either classically-activated (M1) or alternatively-activated (M2), it is now recognised that they exist along a continuum of activation states 8 , with M1 and M2 representing the prototypical pro-and anti-inflammatory extremes of this spectrum 9 .”
From Soft tissue-mimicking hydrogel stiffness modulates polarisation of human monocyte-derived macrophages (2025) · cites this paper as [8]
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- [65]McInnes L, Healy J, and Melville J. Umap: Uniform manifold approximation and projection for dimension reduction. arXiv preprint arXiv:180203426. 2018.
Cited by
Sorted by citations
Coser, C., Ghaemmaghami, A. M., & Yang, J. (2025) · Biomaterials Science · doi:10.1039/d5bm01187f · Cited by 17 · see citing works
- Authors
- Karlinsey, K., Qu, L., Matz, A. J., & Zhou, B.
- Affiliations
- University of Connecticut (US)
- Corresponding author
- Zhou, Beiyan
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-06-21
- Volume
- 112
- Issue
- 6
- Pages
- 1535-1542
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- PMC
- PMC11826963
- OpenAlex
- W4283212618
- Cited by
- 23
- References
- 88
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 9 · 2022: 4
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK121805)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- macrophage polarization, M1/M2 macrophages, adipose tissue macrophages, obesity, cardiovascular disease, atherosclerosis, foam cells, insulin resistance, inflammation, macrophage differentiation
- MeSH terms
- Animals, Anti-Inflammatory Agents, Humans, Inflammation, Insulin Resistance, Macrophages, Obesity, Atherosclerosis, Mice
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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