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CD24 and Siglec-10 Selectively Repress Tissue Damage–Induced Immune Responses
Open accessAbstract
Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. We report that CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1, heat shock protein 70, and heat shock protein 90; negatively regulates their stimulatory activity; and inhibits nuclear factor kappaB (NF-kappaB) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24-Siglec G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns.
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“A clear example of glycan-based SAMPs has been reported in the form of inhibitory Siglec recognition of cell surface sialoglycans (962 -964), which may also provide a mechanism for the host to discriminate between infectious nonself and noninfectious self (965).”
From Biological roles of glycans (2017) · cites this paper as [963]
In the citing paper
“CD24-mediated inhibition was associated with increased pro-inflammatory cytokine production by HMGb1 and decreased survival following acetaminophen-induced liver injury106.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [106]
In the citing paper
“Specifically, CD24, which can bind to both HMGb1 and HSPs, negatively regulates sterile inflammatory responses.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [106]
In the citing paper
“It has also been shown that DAMP-specific receptors can negatively regulate inflammatory responses.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [106]
In the citing paper
“Specifically, CD24, which can bind to both HMGb1 and HSPs, negatively regulates sterile inflammatory responses.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [106]
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“By interacting with Siglec-G/10, an immunoreceptor tyrosine-based inhibition motif (ITIM)-containing negative regulator of inflammation, CD24 has been shown to serve as an essential brake for inflammation induced by damageassociated molecular patterns (DAMPs).(6,7) Bacterial and viral-derived sialidases, which were pr…”
BackgroundThe role of high‐mobility group protein box 1 in lung cancer
Wu, X., Chen, Y., Gong, C., & Pei, D. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26837 · Cited by 18
Li, D., Hu, M., Liu, Y., Du, P., Du, P., Li, C.-S., Cheng, L., Liu, P., Jiang, J., Su, L., et al. (2018) · Cell Discovery · doi:10.1038/s41421-017-0007-9 · Cited by 18
Self-citationEspinosa, D. A., Beatty, P. R., Puerta-Guardo, H. N., Islam, M. N., Belisle, J. T., Perera, R. M., & Harris, E. (2019) · Journal of General Virology · doi:10.1099/jgv.0.001319 · Cited by 18
“For instance, cell inflammatory responses are increased after Sia removal from cell surface ligands or receptors [25].”
BackgroundUpdate on Extracellular Vesicle-Based Vaccines and Therapeutics to Combat COVID-19
Mustajab, T., Kwamboka, M. S., Choi, D. A., Kang, D. W., Kim, J., Han, K. R., Han, Y., Lee, S., Song, D., & Chwae, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911247 · Cited by 18
Ozawa, Y., Harutani, Y., Oyanagi, J., Akamatsu, H., Murakami, E., Shibaki, R., Hayata, A., Sugimoto, T., Tanaka, M., Takakura, T., et al. (2020) · Cancer Science · doi:10.1111/cas.14705 · Cited by 17
Zhang, C., Zhang, J., Liang, F., Guo, H., Gao, S., Yang, F., Guo, H., Wang, G., Wang, W., & Zhou, G. (2022) · Frontiers of Medicine · doi:10.1007/s11684-021-0868-z · Cited by 17
Drug resistance in NSCLC is associated with tumor micro-environment
Zhang, W., Ke, Y., Liu, X., Jin, M., & Huang, G. (2022) · Reproductive Biology · doi:10.1016/j.repbio.2022.100680 · Cited by 17
HMGB1 is a promising therapeutic target for asthma
Zhao, Y., & Li, R. (2023) · Cytokine · doi:10.1016/j.cyto.2023.156171 · Cited by 17
Green, O., Shenberg, G., Baruch, R., Argaman, L., Levin, T., Michelson, I., Hadary, R., Isakovich, B., Golos, M., Schwartz, R., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11092523 · Cited by 17
“CD24, in particular, binds to DAMPs, preventing their interaction with pattern recognition receptors (TLRs) and further inhibiting the activation of the NF-kB pathway [11–13].”
Molecular characterization of porcine Siglec-10 and analysis of its expression in blood and tissues
Escalona, Z., Álvarez, B., Uenishi, H., Toki, D., Yuste, M. T., Revilla, C., del Moral, M. G., Alonso, F., Ezquerra, Á., & Domı́nguez, J. (2014) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2014.09.011 · Cited by 17
Moon, Y. W., An, H. J., Koo, J. S., Kim, G. M., Han, H., Park, S., Kim, S. I., Park, H. S., Kim, S., Kim, S. K., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.23519 · Cited by 17
“[10, 16, 18] Thirdly, a recent study has revealed that CD24 suppresses the immune response through interaction with Siglec protein expressed on immune cells, [19] contributing to cancer immune escape.”
BackgroundBiochemical and molecular characterization of sialylated cervical mucins in sheep
Abril-Parreño, L., Morgan, J., Krogenæs, A., Druart, X., Cormican, P., Gallagher, M. E., Reid, C. J., Meade, K. G., Saldova, R., & Fair, S. (2022) · Biology of Reproduction · doi:10.1093/biolre/ioac077 · Cited by 16
“SIGLEC10 and its ligand CD24 are required to inhibit the production of proinflammatory cytokines [34].”
BackgroundPrecise O-Glycosylation Site Localization of CD24Fc by LC-MS Workflows
Li, X., Wilmanowski, R., Gao, X., VanAernum, Z. L., Donnelly, D. P., Kochert, B. A., Schuessler, H. A., & Richardson, D. D. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.2c01137 · Cited by 16
Yin, S., Li, C., Shen, X., Yu, G., Cui, L., Wu, Y., He, Y., Yu, S., Chen, J., Lu, S., et al. (2024) · Advanced Science · doi:10.1002/advs.202403438 · Cited by 15
Gaskell, H., Ge, X., Désert, R., Das, S., Han, H., Lantvit, D. D., Guzman, G., & Nieto, N. (2019) · Hepatology Communications · doi:10.1002/hep4.1448 · Cited by 16
“(16) Furthermore, hepatocytes exposed to lipids or undergoing cell damage release HMGB1(8,10,11) that can bind to numerous receptors on adjacent cells to evoke downstream pro-inflammatory and pro-fibrogenic processes.(12,17,18) This literature suggests a role for HMGB1 in modulating the response of the liver to high l…”
BackgroundGuo, Q., Song, W., Li, H., Li, M., Chen, X., Liu, H., Peng, H.-L., Yu, H., Liu, N., Lü, Z., et al. (2020) · Respiratory Research · doi:10.1186/s12931-020-01457-2 · Cited by 16
A Guillain-Barré syndrome-associated SIGLEC10 rare variant impairs its recognition of gangliosides
Sheikh, A. A. D., Gomaa, S., Li, X., Routledge, M., Saigoh, K., Numoto, N., Angata, T., Hitomi, Y., Takematsu, H., Tsuiji, M., et al. (2020) · Journal of Autoimmunity · doi:10.1016/j.jaut.2020.102571 · Cited by 16
Soto, P. C., Karris, M., Spina, C. A., Richman, D. D., & Varki, A. P. (2012) · Journal of Molecular Medicine · doi:10.1007/s00109-012-0951-7 · Cited by 16
“Siglec-10, for example, protects host cells against lethal responses to pathological cell death and helps discriminate danger versus pathogen-associated molecular patterns [12].”
BackgroundPalmblad, K., Schierbeck, H., Sundberg, E., Horne, A., Harris, H. E., Henter, J., & Andersson, J. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00308-0 · Cited by 16
“The functional outcome of this interaction is a potent downregulation of critical intracellular signal pathways needed for multiple central inflammatory mechanisms (Chen et al. 2009; Tian et al. 2020).”
BackgroundSalminen, A. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102926 · Cited by 15
Saini, P., Mirji, G., Islam, S. M. S., Simons, L. M., Bhat, S. A., Bonfanti, A. P., Muthumani, K., Agrawal, P., Cassel, J. A., Tang, H., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-25-0977 · Cited by 16
The Involvement of Alarmins in the Pathogenesis of Sjögren’s Syndrome
Sarrand, J., Baglione, L., Parisis, D., & Soyfoo, M. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105671 · Cited by 15
Resolution Potential of Necrotic Cell Death Pathways
Mázló, A., Tang, Y., Jenei, V., Brauman, J., Yousef, H., Bácsi, A., & Koncz, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010016 · Cited by 16
“HMGB1-Siglec10-CD24 or CD52 tri-molecular complex [64] 2.”
BackgroundSialylation: fate decision of mammalian sperm development, fertilization, and male fertility
Yi, S., Feng, Y., Wang, Y., & Ma, F. (2023) · Biology of Reproduction · doi:10.1093/biolre/ioad067 · Cited by 15
“For example, sialic acid–modified proteins abundant in sperm, such as CD24, can interact with SIGLEC10 [185] on the endometrium and SIGLEC9 on neutrophils during leukocyte reaction [151].”
A phase 2 trial of CD24Fc for prevention of graft-versus-host disease
Magenau, J. M., Jaglowski, S. M., Uberti, J. P., Farag, S. S., Riwes, M. M., Pawarode, A., Anand, S. M., Ghosh, M., Maciejewski, J., Braun, T., et al. (2023) · Blood · doi:10.1182/blood.2023020250 · Cited by 15
Self-citationInhaled CD24-Enriched Exosomes (EXO-CD24) as a Novel Immune Modulator in Respiratory Disease
Shapira, S., Schwartz, R., Tsiodras, S., Bar‐Shai, A., Melloul, A., Borsekofsky, S., Peer, M., Adi, N., MacLoughlin, R. J., & Arber, N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010077 · Cited by 15
“This pathway negatively regulates the activity of NF-κ B through the phosphorylation of immunoreceptor tyrosine-based inhibition motif (ITIM) domains associated with SHP-1 and 2 [13,16,17].”
BackgroundLike a Rolling Stone? A Review on Spontaneous Clearance of Hepatitis C Virus Infection
Rzymski, P., Brzdęk, M., Dobrowolska, K., Poniedziałek, B., Murawska-Ochab, A., Zarębska‐Michaluk, D., & Flisiak, R. (2024) · Viruses · doi:10.3390/v16091386 · Cited by 15
“CD24 encodes for glycosylphosphatidylinositol-anchored cell-surface glycoprotein that is expressed by various immune cells and plays an important role in inflammation and regulates innate and adaptive immune responses [94–96].”
BackgroundWong, S. L., To, J., Santos, J., Allam, V. S. R. R., Dalton, J. P., Djordjevic, S. P., Donnelly, S., Padula, M. P., & Sukkar, M. B. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00212 · Cited by 15
Periodontitis Risk Variants at SIGLEC5 Impair ERG and MAFB Binding
Mueller, R., Chopra, A., Dommisch, H., & Schäefer, A. S. (2021) · Journal of Dental Research · doi:10.1177/00220345211049984 · Cited by 15
“Sialoside-based pattern recognition by SIGLEC5 receptors was shown to selectively suppress the immune response to DAMPs, suggesting a mechanism by which aseptic tissue injury and infection are distinguished (Chen et al. 2009).”
BackgroundThe Big Potential of Small Particles: Lipid-Based Nanoparticles and Exosomes in Vaccination
Shimon, M. B., Shapira, S., Seni, J., & Arber, N. (2022) · Vaccines · doi:10.3390/vaccines10071119 · Cited by 18
“CD24 binds Siglec-10, resulting in an activation of the Siglec-10 signaling pathway [66,67].”
BackgroundMyeloid dysregulation and therapeutic intervention in COVID-19
Gu, R., Mao, T., Qiao, L., Su, T. T., & Wang, J. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101524 · Cited by 14
“CD24 represses DAMP-induced immunity by directly trapping DAMPs to prevent agonistic receptor binding and/or by actively suppressing downstream signaling pathways through Siglec-10/G receptor [74,75].”
SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediatorPreprint
Hysenaj, L., Little, S., Kulhanek, K. R., Gbenedio, O. M., Rodriguez, L., Shen, A. S., Lone, J., Lupin-Jimenez, L. C., Bonser, L. R., Serwas, N. K., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.01.446640 · Cited by 15
“Neutralizing antibodies from COVID-19 patients have multiple targets 49, 50 , suggesting that protective immune responses occur that may block interactions of molecules other than the S protein-ACE2 receptor pair.”
Beyond PD‐1/PD‐L1: New Immune Checkpoints and Therapeutic Combinations in Cancer Immunotherapy
Li, Y., Kang, Z., & Du, Y. (2026) · Medicine Bulletin · doi:10.1002/mdb2.70018 · Cited by 18
Danger signals in tumor cells: a risk factor for autoimmune disease?
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Metadata
- Authors
- Chen, G.-Y., Tang, J., Zheng, P., & Liu, Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Zheng, Pan
- Liu, Yang
- Venue
- Science
- Published
- 2009-03-27
- Volume
- 323
- Issue
- 5922
- Pages
- 1722-1725
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2765686
- OpenAlex
- W2158924104
- Cited by
- 786
- References
- 29
- Citations by year
- 2026: 36 · 2025: 51 · 2024: 43 · 2023: 46 · 2022: 55 · 2021: 64 · 2020: 45 · 2019: 23 · 2018: 28 · 2017: 34 · 2016: 47 · 2015: 44 · 2014: 53 · 2013: 58 · 2012: 37
- FWCI
- 22.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01ai064350-15)
- National Cancer Institute (R01CA112001, CA-58033, R01CA058033, CA112001)
- National Institute of Allergy and Infectious Diseases (R01-AI064350, AI064350)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- CD24, Siglec-10, Siglec-G, pattern recognition receptors, damage-associated molecular patterns, pathogen-associated molecular patterns, innate immune regulation, high mobility group box 1, HSP70, HSP90, NF-κB activation, tissue damage
- MeSH terms
- Acetaminophen, Animals, Dendritic Cells, Humans, Immunity, Innate, Inflammation, Lipopolysaccharides, Liver, Necrosis, Receptors, Antigen, B-Cell, Receptors, Cell Surface, Signal Transduction, Cytokines, Protein Structure, Tertiary, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, HMGB1 Protein, Lectins, Immunoprecipitation, Mutant Proteins, Receptors, Pattern Recognition, Mice, CD24 Antigen, Transcription Factor RelA, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Sialic Acid Binding Immunoglobulin-like Lectins
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