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Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice
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The paradigm that macrophages that reside in steady-state tissues are derived from embryonic precursors has never been investigated in the intestine, which contains the largest pool of macrophages. Using fate-mapping models and monocytopenic mice, together with bone marrow chimera and parabiotic models, we found that embryonic precursor cells seeded the intestinal mucosa and demonstrated extensive in situ proliferation during the neonatal period. However, these cells did not persist in the intestine of adult mice. Instead, they were replaced around the time of weaning by the chemokine receptor CCR2-dependent influx of Ly6C(hi) monocytes that differentiated locally into mature, anti-inflammatory macrophages. This process was driven largely by the microbiota and had to be continued throughout adult life to maintain a normal intestinal macrophage pool.
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“Microglia in the developing brain proliferate locally at a low rate and are not normally replaced by other monocytes and macrophages from outside the brain, in contrast to most other tissue-resident macrophages (which also initially originate from yolk sac-derived macrophages, but are partially or fully replaced by fetal liver- or blood monocyte-derived macrophages [Bain et al., 2014, Calderon et”
From A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response (2017) · cites this paper as Bain et al., 2014
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“This does indeed happen, for example in the gut or the dermis (53,54).”
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Metadata
- Authors
- Bain, C. C., Bravo-Blas, A., Scott, C. L., Gomez Perdiguero, E., Geissmann, F., Henri, S., Malissen, B., Osborne, L. C., Artis, D., & Mowat, A. M.
- Affiliations
- University of Glasgow (GB)
- Centre National de la Recherche Scientifique (FR)
- University of Pennsylvania (US)
- Corresponding author
- Mowat, Allan McI
- ORCID
- Venue
- Nature Immunology
- Published
- 2014-08-24
- Volume
- 15
- Issue
- 10
- Pages
- 929-937
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4169290
- OpenAlex
- W1977536320
- Cited by
- 1,178
- References
- 44
- Citations by year
- 2026: 79 · 2025: 80 · 2024: 98 · 2023: 97 · 2022: 106 · 2021: 104 · 2020: 116 · 2019: 94 · 2018: 118 · 2017: 111 · 2016: 81 · 2015: 71 · 2014: 8
- FWCI
- 41.29
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-10-20)
- Open access
- bronze
- doi.org
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (094763, 101853, 089892)
- Tenovus
- University of Glasgow
- Medical Research Council
- National Institute of Allergy and Infectious Diseases (R01AI097333)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- intestinal macrophages, circulating monocytes, CCR2, Ly6Chi monocytes, microbiota, weaning, macrophage homeostasis, anti-inflammatory macrophages, bone marrow-derived macrophages, fate mapping, parabiosis, bone marrow chimeras
- MeSH terms
- CX3C Chemokine Receptor 1, Animals, Animals, Newborn, Antigens, Differentiation, Antigens, Ly, Cell Differentiation, Flow Cytometry, Intestinal Mucosa, Intestines, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Parabiosis, Time Factors, Gene Expression, Bone Marrow Transplantation, Mice, Knockout, Models, Immunological, Receptors, Chemokine, Reverse Transcriptase Polymerase Chain Reaction, CD11b Antigen, Cell Proliferation, Receptors, CCR2
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