ArticleImmunology2022
Siglec-5 is an inhibitory immune checkpoint molecule for human T cells.
Article in Immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Genetic Biomarkers for Periodontal Diseases: A Systematic Review.Journal of clinical periodontology · 2025Pooled it
- Genome-wide association meta-analysis identifies two novel loci associated with dental caries.BMC oral health · 2024Pooled it
- Siglec expression in sentinel lymph nodes in patients with oral squamous cell carcinoma.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Plasma-Derived Extracellular Vesicle-Enriched Fractions as a Potential Source of Biomarkers for Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD): A Shotgun Proteomic Exploration Analysis.Diagnostics (Basel, Switzerland) · 2026Article
- An atlas of human siglecs integrates expression, affinity, and cis/trans sialoglycan recognition profiles.Nature communications · 2026Article
- Writers and readers of sialylation in immunoregulation in cancer.The Journal of biological chemistry · 2026Review
- Diagnostic significance of salivary and glandular siglec-5 in Sjögren disease and non-Sjögren sicca.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Comprehensive Analysis of Immunomodulatory-Related Genes Reveals MAPK14-Associated Myeloid-Derived Suppressor Cells Infiltration in Pediatric Sepsis.Journal of inflammation research · 2026Article
- Siglecs: From Biomodulation to Immunotherapy.Current protein & peptide science · 2026Review
- Integrative Multi-omics Analysis and Mendelian Randomization Reveal Potential Therapeutic Targets and their Stratification in Lung Squamous Cell Carcinoma.Current medicinal chemistry · 2026Article
- Article
- Serum proteome analysis detects early molecular signatures of disease progression in IgA nephropathy.Clinical kidney journal · 2025Article
- An ultrasensitive and modular platform to detect Siglec ligands and control immune cell function.Science advances · 2025Article
- Increase of Inhibitory Siglec receptors on T cells mitigates severe immune reactions during acute viral infections.PNAS nexus · 2025Article
- Exploring Siglecs: Potential Modulators of Immune Cells in Food Allergy and Therapeutic Applications.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2025Review
- Dysregulated Sialylation in Cancer: From Immunosuppressive Microenvironment to Siglec-Targeted Therapeutics.Biomolecules · 2025Review
- Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma.International journal of molecular sciences · 2025Article
- Hypoxia suppressed the Siglec-5 signaling in TAMs via modulating the balance of SHP2/SYK activation in hepatocellular carcinoma.Scientific reports · 2025Article
- TRAIL induces cytokine production via the NFkB2 pathway promoting neutrophil chemotaxis and neutrophil-mediated immune-suppression in triple negative breast cancer cells.Cancer letters · 2025Article
- Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells.Developmental cell · 2025Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a family of immunoglobulin-type lectins that mediate protein-carbohydrate interactions via sialic acids attached to glycoproteins or glycolipids. Most of the CD33-related Siglecs (CD33rSiglecs), a major subfamily of rapidly evolving Siglecs, contain a cytoplasmic signaling domain consisting of the immunoreceptor tyrosine-based inhibitory motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM) and mediate suppressive signals for lymphoid and myeloid cells. While most CD33rSiglecs are expressed by innate immune cells, such as monocytes and neutrophils, to date, the expression of Siglecs in human T cells has not been well appreciated. In this study, we found that Siglec-5, a member of the CD33rSiglecs, is expressed by most activated T cells upon antigen receptor stimulation. Functionally, Siglec-5 suppresses T cell activation. In support of these findings, we found that Siglec-5 overexpression abrogates antigen receptor induced activation of NFAT and AP-1. Furthermore, we show that GBS β-protein, a known bacterial ligand of Siglec-5, reduces the production of cytokines and cytolytic molecules by activated primary T cells in a Siglec-5 dependent manner. Our data also show that some cancer cell lines express a putative Siglec-5 ligand(s), and that the presence of soluble Siglec-5 enhances tumor-cell specific T cell activation, suggesting that some tumor cells inhibit T cell activation via Siglec-5. Together, our data demonstrate that Siglec-5 is a previously unrecognized inhibitory T cell immune checkpoint molecule and suggest that blockade of Siglec-5 could serve as a new strategy to enhance anti-tumor T cell functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.