Astrocyte Crosstalk in CNS Inflammation
Open accessAbstract
Astrocytes control multiple processes in the nervous system in health and disease. It is now clear that specific astrocyte subsets or activation states are associated with specific genomic programs and functions. The advent of novel genomic technologies has enabled rapid progress in the characterization of astrocyte heterogeneity and its control by astrocyte interactions with other cells in the central nervous system (CNS). In this review, we provide an overview of the multifaceted roles of astrocytes in the context of CNS inflammation, highlighting recent discoveries on astrocyte subsets and their regulation. We explore mechanisms of crosstalk between astrocytes and other cells in the CNS in the context of neuroinflammation and neurodegeneration and discuss how these interactions shape pathological outcomes.
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Activated microglia and astrocytes can phagocytize Aβ through multiple receptors to protect neurons, but failure to clear aggregates leads to persistent chronic inflammation and release of proinflammatory/toxic products (cytokines, chemokines, ROS, NO), amplifying immune responses and neurotoxicity.
“Activated microglia and astrocytes can phagocytize Aβ through multiple receptors to protect neurons,33,34 but failure to clear the aggregates leads to persistent chronic inflammation and the release of a variety of proinflammatory and toxic products, including cytokines, chemokines, reactive oxygen species (ROS) and nitric oxide (NO), which amplify immune responses and lead to neurotoxicity.35”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [33]
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Lee, H.-G., Wheeler, M. A., & Quintana, F. J. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00390-x · Cited by 662 · see citing works
Self-citationMicroglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation
Prinz, M., Masuda, T., Wheeler, M. A., & Quintana, F. J. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-110159 · Cited by 584 · see citing works
Self-citationGut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes
Sanmarco, L. M., Wheeler, M. A., Gutiérrez-Vázquez, C., Polonio, C. M., Linnerbauer, M., Pinho-Ribeiro, F. A., Li, Z., Giovannoni, F., Batterman, K. V., Scalisi, G., et al. (2021) · Nature · doi:10.1038/s41586-020-03116-4 · Cited by 331 · see citing works
Self-citationAstrocytic interleukin-3 programs microglia and limits Alzheimer’s disease
McAlpine, C. S., Park, J., Griciuc, A., Kim, E., Choi, S. H., Iwamoto, Y., Kiss, M. G., Christie, K. A., Vinegoni, C., Poller, W. C., et al. (2021) · Nature · doi:10.1038/s41586-021-03734-6 · Cited by 322 · see citing works
Sun, Y., Koyama, Y., & Shimada, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.903455 · Cited by 304 · see citing works
The aryl hydrocarbon receptor and the gut–brain axis
Barroso, A., Mahler, J. V., Fonseca-Castro, P. H., & Quintana, F. J. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-00585-5 · Cited by 152 · see citing works
Self-citationThe Emerging Role of Central and Peripheral Immune Systems in Neurodegenerative Diseases
Zang, X., Chen, S., Zhu, J., Ma, J., & Zhai, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.872134 · Cited by 139 · see citing works
Cell type mapping reveals tissue niches and interactions in subcortical multiple sclerosis lesions
Lerma-Martin, C., Badia-i-Mompel, P., Ramirez Flores, R. O., Sekol, P., Schäfer, P. S. L., Riedl, C. J., Hofmann, A., Thäwel, T., Wünnemann, F., Ibarra-Arellano, M. A., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01796-z · Cited by 76 · see citing works
“AS play critical roles in MS pathogenesis by either propagating inflammation or promoting tissue homeostasis 35,36 .”
Positron emission tomography in multiple sclerosis - straight to the target
Bodini, B., Tonietto, M., Airas, L., & Stankoff, B. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00537-1 · Cited by 74 · see citing works
Human iPSC-derived glia models for the study of neuroinflammation
Stöberl, N., Maguire, E., Salis, E., Shaw, B., & Hall-Roberts, H. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02919-2 · Cited by 71 · see citing works
Guo, Y., Chen, J., Ji, W., Xu, L., Xie, Y., He, S., Lai, C., Hou, K., Li, Z., Chen, G., et al. (2023) · Molecular Therapy Methods & Clinical Development · doi:10.1016/j.omtm.2023.08.021 · Cited by 47 · see citing works
Geladaris, A., Torke, S., & Weber, M. S. (2022) · CNS Drugs · doi:10.1007/s40263-022-00951-z · Cited by 45 · see citing works
Role of Glia-Derived Extracellular Vesicles in Neurodegenerative Diseases
Li, T., Tan, X., Li, S., Al-Nusaif, M., & Le, W. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.765395 · Cited by 33 · see citing works
Li, M., Liu, Z., Wu, Y., Zheng, N., Liu, X., Cai, A., Zheng, D., Zhu, J., Wu, J., Xu, L., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-022-01580-0 · Cited by 26 · see citing works
Kim, J., Kim, S.-J., Jeong, H.-R., Park, J.-H., Moon, M., & Hoe, H.-S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.903309 · Cited by 23 · see citing works
Dinkel, L., Hummel, S., Zenatti, V., Malara, M., Tillmann, Y., Colombo, A., Monasor, L. S., Suh, J. H., Logan, T., Roth, S., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adl4616 · Cited by 22 · see citing works
- Authors
- Linnerbauer, M., Wheeler, M. A., & Quintana, F. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Corresponding author
- Quintana, Francisco J.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 108
- Issue
- 4
- Pages
- 608-622
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC7704785
- OpenAlex
- W3083733923
- Cited by
- 989
- References
- 41
- Citations by year
- 2026: 151 · 2025: 233 · 2024: 212 · 2023: 164 · 2022: 141 · 2021: 86 · 2020: 1 · 2012: 1
- FWCI
- 10.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- International Progressive MS Alliance (F32NS101790, 1K99NS114111)
- Dana-Farber Cancer Institute (T32CA207201)
- National Multiple Sclerosis Society
- National Institutes of Health (AI126880, NS102807, RG4111A1, JF2161-A-5)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- astrocytes, astrocyte heterogeneity, neuroinflammation, neurodegeneration
- MeSH terms
- Animals, Astrocytes, Cell Communication, Central Nervous System, Humans, Inflammation, Models, Neurological
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.
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