The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
CD22 blockade restores homeostatic microglial phagocytosis in ageing brains
Open accessAbstract
Microglia maintain homeostasis in the central nervous system through phagocytic clearance of protein aggregates and cellular debris. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. However, the mechanisms of impaired microglial homeostatic function and the cognitive effects of restoring this function remain unknown. We combined CRISPR-Cas9 knockout screens with RNA sequencing analysis to discover age-related genetic modifiers of microglial phagocytosis. These screens identified CD22, a canonical B cell receptor, as a negative regulator of phagocytosis that is upregulated on aged microglia. CD22 mediates the anti-phagocytic effect of α2,6-linked sialic acid, and inhibition of CD22 promotes the clearance of myelin debris, amyloid-β oligomers and α-synuclein fibrils in vivo. Long-term central nervous system delivery of an antibody that blocks CD22 function reprograms microglia towards a homeostatic transcriptional state and improves cognitive function in aged mice. These findings elucidate a mechanism of age-related microglial impairment and a strategy to restore homeostasis in the ageing brain.
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“restoration of microglial phagocytosis improved cognitive function in aged mice and promoted a homeostatic microglial transcriptional signature78.”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [78]
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“These were strongly enriched for up-regulated genes with immune-modulatory functions (Table S5), including MHC I-mediated antigen presentation, interferon-response, cell adhesion and complement cascade, as well as regulators of mouse microglia activity (Figure 2C) including Cd22 (Pluvinage et al., 2019), Trem2 and Tyrobp (Yeh et al., 2017).”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as Pluvinage et al., 2019
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Citations
Cites
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“The functional decline of aged microglia may result from the upregulation of CD22; thus, the inhibition of CD22 can enhance the clearance of debris and fibrils, including Aβ oligomers, in vivo, and this process may be potentially beneficial for the treatment of AD.(241) Considerable evidence suggests that the use of a…”
Background
Metadata
- Authors
- Pluvinage, J. V., Haney, M. S., Smith, B. A. H., Sun, J., Iram, T., Bonanno, L., Li, L., Lee, D. P., Morgens, D. W., Yang, A. C., Shuken, S. R., Gate, D., Scott, M., Khatri, P., Luo, J., Bertozzi, C. R., Bassik, M. C., & Wyss-Coray, T.
- Affiliations
- Stanford Medicine (US)
- VA Palo Alto Health Care System (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Nature
- Published
- 2019-04
- Volume
- 568
- Issue
- 7751
- Pages
- 187-192
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6574119
- OpenAlex
- W2934339908
- Cited by
- 459
- References
- 71
- Citations by year
- 2026: 44 · 2025: 73 · 2024: 62 · 2023: 70 · 2022: 71 · 2021: 59 · 2020: 54 · 2019: 26
- FWCI
- 23.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (1s10od020141-01)
- National Institute on Aging (F30AG060638, R01AG045034, DP1AG053015)
- National Human Genome Research Institute (T32HG000044)
- National Cancer Institute (R01CA227942)
- National Institute of General Medical Sciences (T32GM120007, T32GM007365, R01GM059907)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- CD22, microglial phagocytosis, brain aging, microglial homeostasis, sialic acid, myelin debris clearance, amyloid-beta oligomers, alpha-synuclein fibrils, cognitive decline, antibody therapy, CRISPR-Cas9 screen, neurodegeneration
- MeSH terms
- CRISPR-Associated Protein 9, Aging, Animals, Brain, Cognition, Female, Homeostasis, Male, Mice, Inbred C57BL, Phagocytosis, Sequence Analysis, RNA, Microglia, N-Acetylneuraminic Acid, Mice, Sialic Acid Binding Ig-like Lectin 2, CRISPR-Cas Systems
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