Convergence between microglia and peripheral macrophages phenotype during development and neuroinflammation
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Differently from other myeloid cells, microglia derive exclusively from precursors originating within the yolk sac and migrate to the CNS under development, without any contribution from fetal liver or postnatal hematopoiesis. Consistent with their unique ontology, microglia may express specific physiological markers, which have been partly described in recent years. Here we wondered whether profiles distinguishing microglia from peripheral macrophages vary with age and under pathology. To this goal, we profiled transcriptomes of microglia throughout the lifespan and included a parallel comparison with peripheral macrophages under physiological and neuroinflammatory settings using age- and sex-matched wild-type and bone marrow chimera mouse models. This comprehensive approach demonstrated that the phenotypic differentiation between microglia and peripheral macrophages is age-dependent and that peripheral macrophages do express some of the most commonly described microglia-specific markers early during development, such as Fcrls, P2ry12, Tmem119, and Trem2. Further, during chronic neuroinflammation CNS-infiltrating macrophages and not peripheral myeloid cells acquire microglial markers, indicating that the CNS niche may instruct peripheral myeloid cells to gain the phenotype and, presumably, the function of the microglia cell. In conclusion, our data provide further evidence about the plasticity of the myeloid cell and suggest caution in the strict definition and application o…
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Peripheral immune cells may replace microglial populations, though this is controversial.
“Peripheral immune cells may also replace microglial populations,5,23,30–32 though this is controversial.”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [30]
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- Authors
- Grassivaro, F., Menon, R., Acquaviva, M., Ottoboni, L., Ruffini, F., Bergamaschi, A., Muzio, L., Farina, C., & Martino, G.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- Vita-Salute San Raffaele University (IT)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2019-12-09
- Volume
- 40
- Issue
- 4
- Pages
- 784-795
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6975289
- OpenAlex
- W2994615204
- Cited by
- 127
- References
- 22
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 13 · 2023: 26 · 2022: 21 · 2021: 27 · 2020: 17
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion, cc-by)
- Funders
- Fondazione Italiana Sclerosi Multipla
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- microglia, peripheral macrophages, neuroinflammation, central nervous system development, age-related gene expression, TREM2, P2Y12 receptor, TMEM119, bone marrow chimeras
- MeSH terms
- Cell Plasticity, Animals, Brain, Cell Differentiation, Inflammation, Macrophages, Membrane Glycoproteins, Membrane Proteins, Phenotype, Receptors, Immunologic, Microglia, Mice, Receptors, Purinergic P2Y12, Transcriptome
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