ArticleThe EMBO journal2015
Immunomodulatory activity of extracellular Hsp70 mediated via paired receptors Siglec-5 and Siglec-14.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
62 citing papers in PubMed, 99 citations in OpenAlex.
- Proteomic and Small RNA Characterization of Extracellular Vesicle-enriched Particles Released from Cultured Host-isolated Symbiodiniaceae.Marine biotechnology (New York, N.Y.) · 2026Article
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- An atlas of human siglecs integrates expression, affinity, and cis/trans sialoglycan recognition profiles.Nature communications · 2026Article
- 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
- Diabetes, Protein Misfolding, and Heat Stress: Molecular Insights and Translational Perspectives.TH open : companion journal to thrombosis and haemostasis · 2026Review
- CSF estrogens' relationships to neuroinflammatory markers and brain networks in middle-aged and older black and white women.Journal of neuroinflammation · 2025Article
- Siglec-14-LGALS3BP glycoimmune axis shapes tumor-associated macrophage polarization and confers poor outcome in colorectal cancer.NPJ precision oncology · 2025Article
- Pathological noise exposure results in elevated levels of extracellular vesicles enriched with Hsp70 in the plasma.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Discovery and characterization of vertebrate sialoglycan-binding proteins.Seminars in immunology · 2025Review
- Hypoxia suppressed the Siglec-5 signaling in TAMs via modulating the balance of SHP2/SYK activation in hepatocellular carcinoma.Scientific reports · 2025Article
- Anti-Heat Shock Protein 70 Autoantibodies from Patients with Idiopathic Pulmonary Fibrosis Epigenetically Enhance Lung Fibroblast Apoptosis Resistance and Bcl-2 Expression.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Environmental stress and hypertension: the disregarded role of HSP70.Journal of human hypertension · 2024Review
- Enhanced resistance to heat and fungal infection in transgenic Trichoderma via over-expressing the HSP70 gene.AMB Express · 2024Article
- Extracellular Heat Shock Protein 70 Increases the Glucocorticoid Receptor and Dual-Specificity Phosphatase 1 via Toll-like Receptor 4 and Attenuates Inflammation in Airway Epithelial Cells.International journal of molecular sciences · 2023Article
- Comparative physiological anthropogeny: exploring molecular underpinnings of distinctly human phenotypes.Physiological reviews · 2023Review
- Recent progress in targeting the sialylated glycan-SIGLEC axis in cancer immunotherapy.Cancer biology & medicine · 2023Review
- Discovery, classification, evolution and diversity of Siglecs.Molecular aspects of medicine · 2023Review
- (Glycan Binding) Activity-Based Protein Profiling in Cells Enabled by Mass Spectrometry-Based Proteomics.Israel journal of chemistry · 2023Article
- HSP70 and Primary Arterial Hypertension.Biomolecules · 2023Review
- Therapeutic targeting of chronic kidney disease-associated DAMPs differentially contributing to vascular pathology.Frontiers in immunology · 2023Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The intracellular chaperone heat-shock protein 70 (Hsp70) can be secreted from cells, but its extracellular role is unclear, as the protein has been reported to both activate and suppress the innate immune response. Potential immunomodulatory receptors on myelomonocytic lineage cells that bind extracellular Hsp70 are not well defined. Siglecs are Ig-superfamily lectins on mammalian leukocytes that recognize sialic acid-bearing glycans and thereby modulate immune responses. Siglec-5 and Siglec-14, expressed on monocytes and neutrophils, share identical ligand-binding domains but have opposing signaling functions. Based on phylogenetic analyses of these receptors, we predicted that endogenous sialic acid-independent ligands should exist. An unbiased screen revealed Hsp70 as a ligand for Siglec-5 and Siglec-14. Hsp70 stimulation through Siglec-5 delivers an anti-inflammatory signal, while stimulation through Siglec-14 is pro-inflammatory. The functional consequences of this interaction are also addressed in relation to a SIGLEC14 polymorphism found in humans. Our results demonstrate that an endogenous non-sialic acid-bearing molecule can be either a danger-associated or self-associated signal through paired Siglecs, and may explain seemingly contradictory prior reports on extracellular Hsp70 action.
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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.