Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction
Open accessAbstract
Microglia are the principal phagocytes that clear cell debris in the central nervous system (CNS). This raises the question, which cells remove cell debris when microglial phagocytic activity is impaired. We addressed this question using Siglech dtr mice, which enable highly specific ablation of microglia. Non‐microglial mononuclear phagocytes, such as CNS‐associated macrophages and circulating inflammatory monocytes, did not clear microglial debris. Instead, astrocytes were activated, exhibited a pro‐inflammatory gene expression profile, and extended their processes to engulf microglial debris. This astrocytic phagocytosis was also observed in Irf8 ‐deficient mice, in which microglia were present but dysfunctional. RNA‐seq demonstrated that even in a healthy CNS, astrocytes express TAM phagocytic receptors, which were the main astrocytic phagocytic receptors for cell debris in the above experiments, indicating that astrocytes stand by in case of microglial impairment. This compensatory mechanism may be important for the maintenance or prolongation of a healthy CNS.
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Plcg2 deficiency leads to a mild inactivation of microglia.
“Considering that microglia depletion leads to compensatory upregulation of astrocytic genes and activity (26, 27), taken together these results strongly suggest that Plcg2 deficiency leads to a mild inactivation of microglia.”
From Multi-omics analyses reveal novel effects of PLCγ2 deficiency in the mouse brain (2023) · cites this paper as [26]
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“Considering that microglia depletion leads to compensatory upregulation of astrocytic genes and activity (26, 27), taken together these results strongly suggest that Plcg2 deficiency leads to a mild inactivation of microglia.”
Result
- Authors
- Konishi, H., Okamoto, T., Hara, Y., Komine, O., Tamada, H., Maeda, M., Osako, F., Kobayashi, M., Nishiyama, A., Kataoka, Y., Takai, T., Udagawa, N., Jung, S., Ozato, K., Tamura, T., Tsuda, M., Yamanaka, K., Ogi, T., Sato, K., & Kiyama, H.
- Affiliations
- Nagoya University (JP)
- Research Institute of Environmental Medicine, Nagoya University (JP)
- JEOL (Japan) (JP)
- Yokohama City University (JP)
- Tohoku University (JP)
- Matsumoto Dental University (JP)
- Weizmann Institute of Science (IL)
- National Institutes of Health (US)
- Kyushu University (JP)
- University of Miyazaki (JP)
- Corresponding author
- Konishi, Hiroyuki
- Kiyama, Hiroshi
- ORCID
- Venue
- The EMBO Journal
- Published
- 2020-09-22
- Volume
- 39
- Issue
- 22
- Pages
- e104464-e104464
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC7667883
- OpenAlex
- W3087501770
- Cited by
- 179
- References
- 18
- Citations by year
- 2026: 20 · 2025: 26 · 2024: 36 · 2023: 43 · 2022: 31 · 2021: 22 · 2020: 1
- FWCI
- 9.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The EMBO Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (17H05743, 16H05117, 19H03395, 16K07055, 19K06904)
- Nasu Foundation
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- microglial dysfunction, microglial ablation, TAM receptors, inflammatory monocytes, astrocyte activation, compensatory mechanisms, pro-inflammatory gene expression
- MeSH terms
- Interferon Regulatory Factor-8, Animals, Astrocytes, Brain, Central Nervous System, Disease Models, Animal, Female, Male, Phagocytosis, Microglia, Mice, Knockout, Interferon Regulatory Factors, Mice
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