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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]
In the citing paper
“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
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979
Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris
The Tabula Muris Consortium, coordination, O., coordination, L., processing, O. C. A., sequencing, L. P. A., analysis, C. D., annotation, C. T., Writing group, Supplemental text writing group, & Principal investigators (2018) · Nature · doi:10.1038/s41586-018-0590-4 · Cited by 2,842
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543
Cited by
Sorted by citations
Items 201–300 of 467
Ethyl pyruvate enhances spontaneous remyelination by targeting microglia phagocytosis
He, Y., An, J., Yin, J.-J., Sui, R., Miao, Q., Ding, Z., Han, Q.-X., Wang, Q., Ma, C., & Xiao, B. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.105929 · Cited by 23
Zhang, G., Shen, Y., Phipps, J., Sun, L., & Ma, S. (2024) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2024.216059 · Cited by 21
“Previous studies have shown that microglia express most of the risk genes associated with AD and CD22 expression is increased in senescent microglia [148].”
Takatori, S., Kondo, M., & Tomita, T. (2025) · Inflammation and Regeneration · doi:10.1186/s41232-025-00383-4 · Cited by 28
“Additionally, aging affects microglial Aβ phagocytic capacity [70, 71].”
Roles of Siglecs in neurodegenerative diseases
Siew, J. J., Chern, Y., Khoo, K., & Angata, T. (2022) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2022.101141 · Cited by 20
Bystanders or not? Microglia and lymphocytes in aging and stroke
Chauhan, A., & Nguyen, J. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.360345 · Cited by 21
“A recent study by Pluvinage et al. (2019) showed inhibition of CD22 promoted myelin debris removal in vitro and central nervous system (CNS) delivery of antibodies against CD22 reprogrammed microglia towards homeostatic transcriptional state and improved cognitive functions in older mice, thus…”
BackgroundInfluentialBrain macrophage senescence in glioma
Li, L., Zhang, T. C., Xiao, M., Lu, Y., & Gao, L. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.07.005 · Cited by 22
Self-citationDistinct patterns of plaque and microglia glycosylation in Alzheimer's disease
Fastenau, C., Bunce, M., Keating, M., Wickline, J. L., Hopp, S. C., & Bieniek, K. F. (2024) · Brain Pathology · doi:10.1111/bpa.13267 · Cited by 20
“…through several different pathways, including activation of SA receptors (Siglecs) like CD22 and CD33 that are associated with aging and AD risk [7 – 9] Therefore, investigating localization of sialylated glycans within the AD brain is a crucial first step to understand the relationship between…”
BackgroundDisruption of hepatocyte Sialylation drives a T cell-dependent pro-inflammatory immune tone
Oswald, D. M., Zhou, J. Y., Jones, M. B., & Cobb, B. A. (2020) · Glycoconjugate Journal · doi:10.1007/s10719-020-09918-y · Cited by 21
“Consistent with this hypothesis, we discovered that both liver and splenic macrophages express CD22, the inhibitory α2,6sialic acid-specific Siglec thought to be B cell-specific [11, 26, 27] until recently reported inmicroglia [28].”
Atypical Cadherin FAT3 Is a Novel Mediator for Morphological Changes of Microglia
Okajima, T., Gu, Y., Teruya, R.-I., Yano, S., Taketomi, T., Sato, B., Chiba, T., & Tsuruta, F. (2020) · eNeuro · doi:10.1523/eneuro.0056-20.2020 · Cited by 20
“Moreover, BV2 cells are used to facilitate investigating the mechanisms of the neuronal disorder, such as Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and stroke (Urushitani et al., 2006; Burguillos et al., 2015; Zhao et al., 2018; Joshi et al., 2019; Pluvinage et al., 2019), indicating th…”
BackgroundInfluentialChen, Z., Mao, Z., Tang, W., Shi, Y., Liu, J., & You, Y. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00517-1 · Cited by 27
“Conversely, CD22, typically a canonical B cell receptor, negatively regulates phagocytosis in aged microglia by interacting with α2,6-linked sialic acid [207].”
InfluentialAge-related alteration in HNE elimination enzymes
Zhang, H., Morgan, T. E., & Forman, H. J. (2021) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2020.108749 · Cited by 20
Multivalent sialic acid materials for biomedical applications
Cao, Y., Song, W., & Chen, X. (2022) · Biomaterials Science · doi:10.1039/d2bm01595a · Cited by 19
Liu, Z., Yu, D., Song, H. L., Postings, M. L., Scott, P., Wang, Z., Ren, J., & Qu, X. (2023) · ACS Nano · doi:10.1021/acsnano.2c11476 · Cited by 19
Fan, P., Lai, H.-Q., Wang, H., Hu, K., Ruan, Y., Ye, J.-R., Wang, S., Peng, Y., He, W., Li, G., et al. (2025) · Cell Death and Differentiation · doi:10.1038/s41418-025-01475-x · Cited by 18
“Although BV2 microglia do not fully recapitulate the features of microglia, they exhibit similar phagocytic machinery [20].”
Pan, T.-T., Sun, Y., Shi, Y.-F., Zhao, M., Khan, N. U., Chen, H., Ji, W., Li, J., Han, L., & Ma, Q. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01840-5 · Cited by 19
“A β oligomers were prepared according to a previously established method [74].”
Cai, L., Liang, Y., Li, X., Fu, R., Niu, X., Jin, Y., Li, Y., Zhang, Y., Ouyang, P., Wang, C., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2504697122 · Cited by 22
“For instance, Cd22 , a canonical B cell receptor, plays critical role in sustaining long - term microglia activation and is closely associated with age - related microglia impairment ( 38 , 39 ).”
Getting on in Old Age: How the Gut Microbiota Interferes With Brain Innate Immunity
Mossad, O., & Blank, T. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.698126 · Cited by 18
Baidoe‐Ansah, D., Sakib, M. S., Jia, S., Mirzapourdelavar, H., Strackeljan, L., Fischer, A., Aleshin, S. E., Kaushik, R., & Dityatev, A. E. (2022) · Cells · doi:10.3390/cells11132033 · Cited by 16
“An involvement of these processes in cognitive decline was also shown [30].”
BackgroundPindiprolu, S. K. S. S., Madhan, J., Srinivasarao, D. A., Dasari, N., Kumar, C. S. P., Katta, C., & Jyothi, V. G. S. S. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104617 · Cited by 18
Yu, Y., Li, S., Kong, L., Du, Y., Liu, Y., Zang, J., Guo, R., Zhang, L., Zhao, Z., Ju, R.-J., et al. (2023) · Journal of Liposome Research · doi:10.1080/08982104.2023.2290050 · Cited by 18
Alberto García, S., Palacio, A. L., Román, J. F. R., Casamayor, J. C., & Pastor, Ó. (2021) · IEEE Access · doi:10.1109/access.2021.3128757 · Cited by 19
“The default role of this protein is to disrupt microglia cell function, but an altered role causes detritus accumulation in the brain, which produces Alzheimer’s [43], [63].”
BackgroundSimultaneous Detection of Herpes Simplex Virus Type 1 Latent and Lytic Transcripts in Brain Tissue
Zhang, S., Zeng, J., Zhou, Y., Gao, R., Rice, S., Guo, X., Liu, Y., Feng, P., & Zhao, Z. (2022) · ASN NEURO · doi:10.1177/17590914211053505 · Cited by 16
Shui, M., Sun, Y., Lin, D., Xue, Z., Liu, J., Wu, A., & Wei, C. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.788675 · Cited by 18
Microglia in a Dish—Which Techniques Are on the Menu for Functional Studies?
Aktories, P., Petry, P., & Kierdorf, K. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.908315 · Cited by 16
Wang, H., Yang, W. H., Xu, L., Han, Y., Lin, Y., Lu, C., Kim, K., Zhao, Y., & Yu, X. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202400125 · Cited by 17
Advances in understanding and exploiting Siglec–glycan interactions
Jame-Chenarboo, Z., Gray, T. E., & Macauley, M. S. (2024) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2024.102454 · Cited by 17
Yuan, H., Yang, J., Qin, G., Sun, Y., Zhao, C., Wang, C., Ren, J., & Qu, X. (2024) · Chemical Science · doi:10.1039/d4sc04453c · Cited by 17
Inhalable Ce Nanozyme‐Backpacked Phage Aims at Ischemic Cerebral Injury by M1‐Microglia Hitchhiking
Zhu, Z., Jin, L., Wang, Q., Shi, H., Cheng, K., & Mao, Z. (2025) · Advanced Materials · doi:10.1002/adma.202419903 · Cited by 16
Ennerfelt, H. E., Holliday, C., Shapiro, D. A., Zengeler, K. E., Bolte, A. C., Ulland, T. K., & Lukens, J. R. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2303760120 · Cited by 16
“org microglial receptors in mice and humans has uncovered several potential therapeutic targets (85–87); the activation or inhibition of these receptors has dominated microglia- targeted AD therapy as they extensively influence microglial response to AD pathology (6, 14, 20, 22, 32, 35, 59).”
BackgroundA unified model of dementias and age‐related neurodegeneration
Fossel, M. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12012 · Cited by 16
Quarta, A., Berneman, Z. N., & Ponsaerts, P. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ru0820-536r · Cited by 17
Selective agonism of GPR34 stimulates microglial uptake and clearance of amyloid β fibrils
Etani, H., Takatori, S., Wang, W., Omi, J., Amiya, Y., Akahori, A., Watanabe, H., Sonn, I., Okano, H., Hara, N., et al. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01891-8 · Cited by 16
“S11) [45–47], suggesting that an age-related decline in microglial GPR34 expression may be a conserved phenomenon across species.”
Parsi, S., Zhu, C., Motlagh, N. J., Kim, D., Kuellenberg, E. G., Kim, H.-H., Gillani, R. L., & Chen, J. W. (2024) · Magnetic Resonance Imaging Clinics of North America · doi:10.1016/j.mric.2024.01.003 · Cited by 15
Strategies to dissect microglia-synaptic interactions during aging and in Alzheimer's disease
Heuer, S. E., Bloss, E. B., & Howell, G. R. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.109987 · Cited by 16
Emerging microglial biology highlights potential therapeutic targets for Alzheimer's disease
Fan, X., Chen, H., He, W., & Zhang, J. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102471 · Cited by 16
Chronological versus immunological aging: Immune rejuvenation to arrest cognitive decline
Basurco, L., Abellanas, M. A., Purnapatre, M., Antonello, P., & Schwartz, M. (2024) · Neuron · doi:10.1016/j.neuron.2024.12.004 · Cited by 17
Sun, P., Hu, Y., Xing, Q., Deng, W., Ou, Y., Pan, G., Zhong, X., & Hu, W. (2020) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.0c00073 · Cited by 15
Li, L., Yerra, L. P., Chang, B., Mathur, V., Nguyen, A., & Luo, J. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.01.022 · Cited by 16
Self-citationSenescent macrophages in tumor: phenotypes, roles, and interventions
Shen, W., Huang, Y., Yang, X., Zhang, Y., Pan, Y., Xiao, Y., Wang, J., Wang, C., Mao, W., & Zhao, A. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-08000-5 · Cited by 16
“These fi ndings implicate CD22 as a negative regulator of microglial phagocytic activity in the central nervous system, highlighting its potential involvement in the pathogenesis of age-related neurodegenerative disorders [85].”
Lai, Z., Ye, T., Zhang, M., & Mu, Y. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s484119 · Cited by 15
“78,79 Studies have indicated that neurons can inhibit the activation of microglia and promote their polarization towards the M2 phenotype.”
BackgroundImpact of aging on gene expression response to x-ray irradiation using mouse blood
Broustas, C. G., Duval, A. J., & Amundson, S. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-89682-7 · Cited by 13
Liu, H.-J., Wang, M., Wang, Y., Shi, S., Hu, X., Zhang, D.-B., Fan, D., Mintzer, J., & Xu, P. (2025) · Cell Biomaterials · doi:10.1016/j.celbio.2025.100158 · Cited by 13
Glycan-Binding Proteins in Immunity
Rabinovich, G. A., Rademacher, C., Schattner, M. A., & Macauley, M. S. (2026) · Annual Review of Immunology · doi:10.1146/annurev-immunol-083024-030822 · Cited by 14
Sanchez-Molina, P., Almolda, B., Benseny‐Cases, N., González, B., Perálvarez‐Marín, A., & Castellano, B. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.03.015 · Cited by 14
Samuels, J. D., Lukens, J. R., & Price, R. J. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15981 · Cited by 13
“…SHIP-1 and SHP-1, which can ultimately promote downstream inhibition of ITAM-and SYK-mediated signaling (Angata et al., 2002 ; Crocker & Redelinghuys, 2008; Linnartz et al., 2010 ; Malik et al., 2015; Pluvinage et al., 2019 ; Rawal & Zhao, 2021 ; Siddiqui et al., 2019; Wißfeld et al., 2021 ).”
InfluentialMaeda, C., & Tsuruta, F. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084443 · Cited by 13
“Concerning the age-related loss of phagocytic capacity, the normal B cell receptor CD22 has been identified as a negative regulator of phagocytosis [47].”
BackgroundZhao, Y., Peng, Y., Wei, X., Wu, G., Li, B., Li, X., Long, L., Zeng, J., Luo, W., Tian, Y., et al. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00060 · Cited by 13
Shea, J. M., & Villeda, S. (2025) · eLife · doi:10.7554/elife.97671.3 · Cited by 13
Su, P., Zhang, J., Wu, J., Chen, H., Luo, W., & Hu, M. (2023) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2023.115058 · Cited by 13
Marker, D. F., Kofler, J., Mettenburg, J., Agha, M., & Wiley, C. A. (2020) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlaa099 · Cited by 13
“Although CD22 is predominantly expressed on B cells, recent studies in mice have demonstrated microglial expression of CD22, particularly in aged and activated microglia (18).”
BackgroundRebelo, A. L., Chevalier, M. T., Russo, L., & Pandit, A. S. (2021) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2021.100321 · Cited by 14
Neuron–Microglia Contacts Govern the PGE2 Tolerance through TLR4-Mediated de Novo Protein Synthesis
Kuo, H., Lee, K.-F., Chen, S., Chiu, S.-C., Lee, L., Chen, W.-P., Chen, C., & Chu, C. (2022) · Biomedicines · doi:10.3390/biomedicines10020419 · Cited by 13
“Overall, these humoral or contacts signals from neurons not only lead microglia to prune neural synapses and neurites, and remove the apoptotic neurons during early brain development [45,47], but they also modulate motility, surveillance, and immunity of microglia at inflammatory conditions [44,46,48].”
BackgroundShea, J. M., & Villeda, S. (2024) · eLife · doi:10.7554/elife.97671 · Cited by 18
CD47 inhibits phagocytosis through Vav dephosphorylation
Miller, W. D., Manion, A., Mishra, A. K., Sheedy, C. J., Bond, A., Gardner, B. M., Montell, D. J., & Morrissey, M. A. (2025) · The Journal of Cell Biology · doi:10.1083/jcb.202502206 · Cited by 13
State-specific enhancer landscapes govern microglial plasticity
Hamagami, N., Kapadia, D., Barclay, K. M., Yanlong, H., Abduljawad, N., Cheng, Z., McLaughlin, L., Singhania, D., Ding, X., Yang, J., et al. (2026) · Immunity · doi:10.1016/j.immuni.2025.11.023 · Cited by 20
Shen, Z., Yang, X., Lan, Y., & Chen, G. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231159 · Cited by 13
Microglial Lyzl4 Facilitates β‐Amyloid Clearance in Alzheimer's Disease
Pan, J., Zhong, J., Geng, J., Oberhauser, J., Shi, S., & Wan, J. (2024) · Advanced Science · doi:10.1002/advs.202412184 · Cited by 11
Biochemical and biophysical mechanisms macrophages use to tune phagocytic appetite
Bond, A., & Morrissey, M. A. (2025) · Journal of Cell Science · doi:10.1242/jcs.263513 · Cited by 12
Deglycosylation of SLAMF7 in breast cancers enhances phagocytosis.
Wang, S.-H., Chou, W., Huang, H., Lee, T.-A., Hsiao, T., Wang, L., Huang, K.-B., Kuo, C., Chao, C.-H., Chang, S., et al. (2022) · PubMed Central · Cited by 12
Lv, J., Shen, X., Shen, X.-Y., Zhao, S., Xu, R., Yan, Q., Lu, J., Zhu, D., Zhao, Y., Dong, J., et al. (2023) · Phytotherapy Research · doi:10.1002/ptr.7945 · Cited by 12
“To maintain homeostasis in the CNS, microglia recognise, engulf, and degrade extracellular protein aggregates and debris via phagocytosis (Pluvinage et al., 2019).”
Transgenic mouse models to study the physiological and pathophysiological roles of human Siglecs
McCord, K. A., & Macauley, M. S. (2022) · Biochemical Society Transactions · doi:10.1042/bst20211203 · Cited by 12
Multiple Sclerosis and Other Acquired Demyelinating Diseases of the Central Nervous SystemPreprint
Kornberg, M. D., & Calabresi, P. A. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041374 · Cited by 17
Immune cells in intracerebral hemorrhage
Taşkin, I. Ç., & Yao, Y. (2025) · Brain Hemorrhages · doi:10.1016/j.hest.2025.02.001 · Cited by 11
“56 Similarly, blockade of CD22, a negative regulator of microglial homeostasis, 57 improves cognitive function and behavioral recovery and reduces secondary brain injury in mice after ICH by shifting microglia to a reparative state, enhancing phagocytosis, reducing inflammation, and limiting…”
Exosomal miRNAs as Biomarkers of Ischemic Stroke
Ciaccio, A. M., & Tuttolomondo, A. (2023) · Brain Sciences · doi:10.3390/brainsci13121647 · Cited by 14
“Some authors showed that neuron-derived sEV could induce M2-type microglia polarization [67,68].”
BackgroundMcComb, S., Arbabi‐Ghahroudi, M., Hay, K. A., Keller, B. A., Faulkes, S., Rutherford, M., Nguyen, T., Shepherd, A., Wu, C., Marcil, A., et al. (2024) · Molecular Therapy Oncology · doi:10.1016/j.omton.2024.200775 · Cited by 12
“Given the known risk of immune effector cell-associated neurotoxicity syndrome with CD22-CAR therapies 25 and data showing that CD22 expression can be detected in aging human and mouse microglia, 26,27 brain assessments were of particular importance.”
BackgroundElevated phagocytic capacity directs innate spinal cord repair
Shaw, D. K., Saraswathy, V. M., McAdow, A. R., Zhou, L., Park, D., Mote, R. D., Saini, A., Douthitt, A. J., Stepankova, K., Unverzagt, B., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117482 · Cited by 12
CD22 blockade exacerbates neuroinflammation in Neuromyelitis optica spectrum disorder
Zhang, W., Han, Y., Huang, H., Su, Y., Ren, H., Qi, C., Li, J., Yang, H., Xu, J., Chang, G., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03305-2 · Cited by 11
The regulation of microglia by aging and autophagy in multiple sclerosis
Wang, X., Sun, Y., Yu, H., Xue, C., Pei, X., Chen, Y., & Guan, Y. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107786 · Cited by 11
Xu, X., Wang, H., Bennett, D. A., Zhang, Q., Wang, G., & Zhang, H. (2022) · Biomedicines · doi:10.3390/biomedicines10081782 · Cited by 11
“CD22 inhibition increases microglial phagocytosis of Aβ oligomers and ameliorates cognitive impairment in elderly mice [50].”
BackgroundCirculatory proteins shape microglia state and boost phagocytosisPreprint
Lu, N., Losada, P. M., Hahn, O., Saksena, A., Tapp, E., Chadarevian, J. P., Dong, W., Shi, S. M., Shuken, S. R., Guldner, I. H., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.30.615861 · Cited by 12
Self-citationNegredo, P. N., You, J., Hauptschein, M., Schroer, A. B., Richard, D. J., Abhiraman, G. C., Tsai, A. P., Sun, E., Notarangelo, G., Ramirez-Matias, J., et al. (2026) · Immunity · doi:10.1016/j.immuni.2026.01.016 · Cited by 12
Self-citationAge-dependent Microglial Disease Phenotype Results in Functional Decline in Gut Macrophages
Bishop, E. S., Namkoong, H., Aurelian, L., McCarthy, M., Nallagatla, P., Zhou, W., Neshatian, L., Gurland, B., Habtezion, A., & Becker, L. S. (2022) · Gastro Hep Advances · doi:10.1016/j.gastha.2022.09.006 · Cited by 10
“GS MMs also exhibited increased CD22 expression that, similar to microglia, 35 resulted in the loss of phagocytic activity (Figure 3E).”
BackgroundMethodPotential Alzheimer’s disease drug targets identified through microglial biology research
Lepiarz‐Raba, I., Hidayat, T., Hannan, A. J., & Jawaid, A. (2024) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2024.2335210 · Cited by 9
“Furthermore, CNS delivery of a CD22-blocking antibody enhanced phagocytosis of injected Aβ oligomers, restored microglial homeostasis, and rescued spatial memory in mice [124].”
BackgroundThe emerging links between immunosenescence in innate immune system and neurocryptococcosis
Soraci, L., Beccacece, A., Princiotto, M., Savedra, E. V., Gambuzza, M. E., Aguennouz, M., Corsonello, A., Luciani, F., Muglia, L., Filicetti, E., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1410090 · Cited by 11
Tauroursodeoxycholic acid targets HSP90 to promote protein homeostasis and extends healthy lifespan
Liu, J., Wang, Y., Guo, Y., Zheng, R.-Q., Wang, Y., Shen, Y., Liu, Y., Cao, A.-P., Wang, R., Xie, B.-Y., et al. (2024) · Science China Life Sciences · doi:10.1007/s11427-024-2717-6 · Cited by 13
“Based on these findings, extensive efforts have been dedicated to discovering novel anti-aging molecules over the past two decades (Chin et al., 2014; Pluvinage et al., 2019; Smith et al., 2015; Yousef et al., 2019).”
Ageing-related changes in the regulation of microglia and their interaction with neurons
Rommy von Bernhardi, M., & Eugenín, J. L. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110241 · Cited by 10
Sirerol-Piquer, M. S., Pérez‐Villalba, A., Duart-Abadía, P., Belenguer, G., Gómez‐Pinedo, U., Blasco-Chamarro, L., Carrillo-Barberà, P., Pérez‐Cañamás, A., Navarro, V., Dehay, B., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00816-1 · Cited by 12
“Its blockade promotes the clearance of αSyn fibrils in vivo, among other substrates, but also partially reverses the transcriptional signature of aged microglia towards that of a more homeostatic state [77].”
Alzheimer’s Disease Progression in the 5×FAD Mouse Captured with a Multiplex Gene Expression Array
Gatt, A. P., Whitfield, D., Ballard, C. G., Doherty, P., & Williams, G. H. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190805 · Cited by 8
“Interestingly, a recent study high-lighted how a normal age-related loss in the ability to clear debris might contribute to the onset of AD [54].”
Roles of Microglia in AD Pathology
Gao, R., Wu, H., Li, Q., & Zhao, J. (2023) · Current Alzheimer Research · doi:10.2174/1567205020666230203112351 · Cited by 10
Regulators of phagocytosis as pharmacologic targets for stroke treatment
Cheng, J. G., Wang, W., Xia, Y., Li, Y., Jia, J., & Xiao, G. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1122527 · Cited by 10
“CD22mediates the antiphagocytic effect of α2–6-linked sialic acid, and CNS delivery of a CD22 function-blocking antibody promotes the clearance of myelin debris, amyloid-β oligomers, and αsynuclein fibrils in vivo by reprogramming microglia toward a homeostatic transcriptional state (Pluvinage et al., 2019).”
BackgroundTissue-specific features of microglial innate immune responses
Timmerman, R., Burm, S. M., & Bajramovic, J. J. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104924 · Cited by 10
Wickstead, E. S., Irving, M. A., Getting, S. J., & McArthur, S. (2021) · FEBS Journal · doi:10.1111/febs.15861 · Cited by 10
Oligomeric amyloid beta prevents myelination in a clusterin-dependent mannerPreprint
Beiter, R. M., Ennerfelt, H. E., Rivet-Noor, C. R., Merchak, A. R., Bai, R., Johanson, D. M., Slogar, E. R., Sol‐Church, K., Phillips, J. L., Bathe, T., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.06.981373 · Cited by 11
Huang, Y., & Zhu, Z. (2022) · Ibrain · doi:10.1002/ibra.12021 · Cited by 9
Tsubata, T. (2023) · International Immunology · doi:10.1093/intimm/dxad030 · Cited by 10
Wang, X., Liu, L., Jiang, X., Saredy, J., Xi, H., Cueto, R., Sigler, D., Khan, M., Wu, S., Ji, Y. H., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01311-9 · Cited by 8
“Supplemental knockout phagocytic MG cell line screening dataset [50] with above-identified human and mouse AD MG DEG.”
BackgroundInfluentialCD22 blockade aggravates EAE and its role in microglia polarization
Xiang, W., Wang, K., Han, L., Wang, Z., Zhou, Z., Bai, S., Peng, J., Xie, C., & Guan, Y. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14736 · Cited by 8
“18 To date, little is known about whether CD22 may affect neuroin-flammation following MS.”
BackgroundInfluentialA Gene Cluster of Mitochondrial Complexes Contributes to the Cognitive Decline of COVID-19 Infection
Xu, W., An, X., Chen, M.-J., Ma, J., Wang, X.-Q., Yang, J.-N., Wang, Q., Wang, D., Wu, Y., Zeng, L., et al. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04471-3 · Cited by 8
“CD22 inhibits microglial phagocytosis of damaged cells [42].”
Siglecs-mediated immune regulation in neurological disorders
Tu, H., Yuan, L., Ni, B., Lin, Y., & Wang, K. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107531 · Cited by 9
M2 ‐Like Macrophages Exhibit Sialic Acid‐Enhanced Efferocytosis via the Siglec CD22
Kukan, E. N., Fabiano, G. L., Glendenning, L. M., Zhou, J. Y., Telfer, K., Paulson, J. C., & Cobb, B. A. (2025) · The FASEB Journal · doi:10.1096/fj.202500146rr · Cited by 9
“Although macrophages are known to express other members of the Siglec family, such as Siglec-1 (sialoadhesin; CD169) [29], Siglec-F [30], Siglec-9 [31], and Siglec-10 [32, 33], the presence of CD22 has only been reported twice, both times in microglia [34, 35].”
Bertoni, G., Ristori, S., & Monti, D. (2026) · Cells · doi:10.3390/cells15080657 · Cited by 10
Interrogation of human microglial phagocytosis by CRISPR genome editing
Chang, J. C.-Y., Wang, C., & Lin, S. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1169725 · Cited by 9
“The higher the score (1-100) indicates the higher predicted efficiency (B) The % of CD40-negative cells and viability were measured by flow cytometry, and the % of insertion-deletion (indel) was determined by Sanger DNA sequencing and ICE analysis.”
MethodFriends and Foes in Alzheimer’s Disease
Pauwels, E. K. J., & Boer, G. J. (2023) · Medical Principles and Practice · doi:10.1159/000534400 · Cited by 10
“The long-term inhibition of C22 promotes clearance of β A in vivo and reprograms microglia toward the M2 state and improves the cognitive function of these mice [33].”
BackgroundLu, M., Hao, C., Xu, L., Feng, Y., Jiang, J., Wang, Y., Xu, J., Kuang, H., Xu, C., & Sun, M. (2024) · Science China Chemistry · doi:10.1007/s11426-023-1859-4 · Cited by 9
Circadian rhythm and neurodegenerative disorders
Werdann, M., & Zhang, Y. (2020) · Brain Science Advances · doi:10.26599/bsa.2020.9050006 · Cited by 9
Li, Z., Wu, J., Zhao, T., Wei, Y., Xu, Y., Liu, Z., Li, X., & Chen, X. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1296205 · Cited by 9
“CD22, a canonical B-cell receptor, was upregulated in aging microglia and involved in antiphagocytosis (Pluvinage et al., 2019).”
BackgroundMicroglia and Microbiome-Gut-Brain Axis
Filho, A. M. C., Gomes, N. S., Lós, D. B., Leite, I. B., Tremblay, M., & Macêdo, D. S. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-55529-9_17 · Cited by 8
Senescent microglia: The hidden culprits accelerating Alzheimer’s disease
Li, W., Xie, Y., Jia-Xin, M., Shu-Chao, G., & Li-Ping, H. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149480 · Cited by 11
Macrophage-centered therapy strategies: A promising weapon in cancer immunotherapy
Wang, S., Liu, J., Cui, Y., Sun, M., Wang, W., Chen, J., Gu, J., & Yang, Z. (2025) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2025.101063 · Cited by 10
“However, the specific mechanisms underlying their role in phagocytosis require further investigation [ 117 ].”
Syntaxin-2 balances phagocytic uptake and phagolysosomal clearance in macrophages
Samanta, S., Nandi, A., Datta, R., & Dolai, S. (2025) · Journal of Cell Science · doi:10.1242/jcs.263855 · Cited by 8
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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