ArticleThe Journal of experimental medicine2002
Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4.
Article in The Journal of experimental medicine, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 509 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
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
509 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,362 citations in OpenAlex.
- Pooled it
- Pooled it
- Trained immunity in chronic, relapsing and low-grade joint inflammation.Nature reviews. Rheumatology · 2026Review
- Naive CD4iScience · 2026Article
- Blue®m gel vs hyaluronic acid gel in wound healing and pain control following functional crown lengthening: a randomized controlled trial.The Saudi dental journal · 2026Article
- Structural insights into glycan recognition by plant immune receptors: a comparative perspective with animal innate immune systems.The Plant journal : for cell and molecular biology · 2026Review
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Comparative Genomic and Functional Profiling of ECM-Targeting Enzymes inbioRxiv : the preprint server for biology · 2026Article
- The Emerging Role of Hyaluronic Acid as a Multifunctional Regenerative Agent in Periodontal Healing.Gels (Basel, Switzerland) · 2026Review
- Hyaluronan 35 prevents endotoxin-mediated dysregulated skeletal muscle proteostasis during ethanol exposure.American journal of physiology. Endocrinology and metabolism · 2026Article
- Development and characterization of a model of mucopolysaccharidosis type IVA for evaluating therapies targeting bone disease.Disease models & mechanisms · 2026Article
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- The Extracellular Matrix and the Immune System in Acute Lung Injury: Partners in Damage and Repair.Biomedicines · 2025Review
- The Immobilization of Hyaluronic Acid in 3D Hydrogel Scaffolds Modulates Macrophage Polarization.Advanced biology · 2025Article
- Empowering chemotherapy-induced antitumor immunity by multi-targeted synergistic combination nanomedicine for triple-negative breast cancer.Materials today. Bio · 2025Article
- Neuroinflammation as a Novel Therapeutic Frontier for Sanfilippo Syndrome.Children (Basel, Switzerland) · 2025Review
- Hyaluronic Acid in Liver Fibrosis: Role in Inflammation, Tissue Remodeling, and Disease Progression.International journal of molecular sciences · 2025Review
- Catalytic Site Inhibitors of Group 1 Allergens Prevent Toll-like Receptor (TLR)4- and TLR1/2-Dependent Innate Responses in Keratinocytes and Airway Epithelial Cells Exposed to House Dust Mite Allergenic Extract.ACS pharmacology & translational science · 2025Article
- CD44 signaling in skin wound healing and regeneration.Journal of translational medicine · 2025Review
- Revitalizing Colchicine: Novel Delivery Platforms and Derivatives to Expand Its Therapeutic Potential.International journal of molecular sciences · 2025Review
449 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like receptor (TLR)-4, a receptor complex associated with innate immunity and host defense against bacterial infection. Bone marrow-derived DCs from C3H/HeJ and C57BL/10ScCr mice carrying mutant TLR-4 alleles were nonresponsive to sHA-induced phenotypic and functional maturation. Conversely, DCs from TLR-2-deficient mice were still susceptible to sHA. In accordance, addition of an anti-TLR-4 mAb to human monocyte-derived DCs blocked sHA-induced tumor necrosis factor alpha production. Western blot analysis revealed that sHA treatment resulted in distinct phosphorylation of p38/p42/44 MAP-kinases and nuclear translocation of nuclear factor (NF)-kappa B, all components of the TLR-4 signaling pathway. Blockade of this pathway by specific inhibitors completely abrogated the sHA-induced DC maturation. Finally, intravenous injection of sHA-induced DC emigration from the skin and their phenotypic and functional maturation in the spleen, again depending on the expression of TLR-4. In conclusion, this is the first report that polysaccharide degradation products of the extracellular matrix produced during inflammation might serve as an endogenous ligand for the TLR-4 complex on DCs.
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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.