Tissue-specific signals control reversible program of localization and functional polarization of macrophages
Open accessAbstract
Tissue-resident macrophages are highly heterogeneous in terms of their functions and phenotypes as a consequence of adaptation to different tissue environments. Local tissue-derived signals are thought to control functional polarization of resident macrophages; however, the identity of these signals remains largely unknown. It is also unknown whether functional heterogeneity is a result of irreversible lineage-specific differentiation or a consequence of continuous but reversible induction of diverse functional programs. Here, we identified retinoic acid as a signal that induces tissue-specific localization and functional polarization of peritoneal macrophages through the reversible induction of transcription factor GATA6. We further found that GATA6 in macrophages regulates gut IgA production through peritoneal B-1 cells. These results provide insight into the regulation of tissue-resident macrophage functional specialization by tissue-derived signals.
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Tissue macrophage specialization is largely determined by cues from the local tissue environment.
“Tissue macrophage specialization is dictated largely by tissue-specific environmental cues (Bruttger et al., 2015; Lavin et al., 2015; Okabe and Medzhitov, 2014).”
From Diverse Requirements for Microglial Survival, Specification, and Function Revealed by Defined-Medium Cultures (2017) · cites this paper as Okabe and Medzhitov, 2014
The Discussion (page unavailable) shows that local tissue-derived signals, including retinoic acid, control a peritoneal macrophage-specific program and a subset of its functions. The Introduction suggests that such signals may shape macrophage phenotypes across tissues, but the paper does not establish that environmental cues largely dictate tissue macrophage specialization in general. (LLM, conf=0.83)
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- Authors
- Okabe, Y., & Medzhitov, R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Medzhitov, Ruslan
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 157
- Issue
- 4
- Pages
- 832-844
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4137874
- OpenAlex
- W2068714945
- Cited by
- 884
- References
- 14
- Citations by year
- 2026: 41 · 2025: 58 · 2024: 58 · 2023: 66 · 2022: 64 · 2021: 85 · 2020: 84 · 2019: 84 · 2018: 84 · 2017: 86 · 2016: 76 · 2015: 68 · 2014: 29
- FWCI
- 36.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Promotion and Mutual Aid Corporation for Private Schools of Japan
- National Institutes of Health (UL1TR000142)
- National Cancer Institute (R01CA157461, CA157461)
- National Institute of Allergy and Infectious Diseases (AI089771, R01AI089771, R37AI046688, AI046688, R01AI046688)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK071754)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- tissue-resident macrophages, retinoic acid, GATA6, peritoneal macrophages, B-1 cells, macrophage heterogeneity
- MeSH terms
- Animals, Gene Expression Regulation, Immunoglobulin A, Mice, Inbred C57BL, Omentum, Tretinoin, Macrophages, Peritoneal, GATA6 Transcription Factor, 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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