ArticleThe Journal of biological chemistry2014
Selective antibody intervention of Toll-like receptor 4 activation through Fc γ receptor tethering.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis 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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective.Experimental & molecular medicine · 2024Pooled it
- IMGT-NC Engineered Variants of INN Therapeutic IG or Antibodies and Related IgSF Proteins (TR, FPIA and CPCA): Bridging Sequences, Structures and Functions for AI.Biomolecules · 2026Review
- Nanocluster-mediated signaling crosstalk between FcγR and TLR4 in macrophage inflammatory responses.Scientific reports · 2025Article
- Real-time monitoring with iTLR4 assay identifies ligand-dependent TLR4-TLR4 conformational dynamics.Frontiers in immunology · 2025Article
- Inhibition of TLR4 signalling to dampen joint inflammation in osteoarthritis.Rheumatology (Oxford, England) · 2024Review
- AL008 Enhances Myeloid Antitumor Function by Inhibiting SIRPα Signaling and Activating Fc Receptors.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- IMGTAntibodies (Basel, Switzerland) · 2022Article
- Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies.International journal of molecular sciences · 2021Article
- Phenotype and Response to PAMPs of Human Monocyte-Derived Foam Cells Obtained by Long-Term Culture in the Presence of oxLDLs.Frontiers in immunology · 2020Article
- Monoclonal Antibody to CD14, TLR4, or CD11b: Impact of Epitope and Isotype Specificity on ROS Generation by Human Granulocytes and Monocytes.Oxidative medicine and cellular longevity · 2020Review
- Boosting therapeutic potency of antibodies by taming Fc domain functions.Experimental & molecular medicine · 2019Review
- TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts.The Journal of biological chemistry · 2019Article
- Targeting early changes in the synovial microenvironment: a new class of immunomodulatory therapy?Annals of the rheumatic diseases · 2019Article
- Molecular mechanisms of macrophage Toll-like receptor-Fc receptor synergy.F1000Research · 2018Review
- IgG Fc engineering to modulate antibody effector functions.Protein & cell · 2018Review
- Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation.Nature communications · 2017Article
- Oxidized Low-Density Lipoprotein Immune Complex Priming of the Nlrp3 Inflammasome Involves TLR and FcγR Cooperation and Is Dependent on CARD9.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2017Review
- Tlr2 on Bone Marrow and Non-Bone Marrow Derived Cells Regulates Inflammation and Organ Injury in Cooperation with Tlr4 During Resuscitated Hemorrhagic Shock.Shock (Augusta, Ga.) · 2016Article
- A specific anti-citrullinated protein antibody profile identifies a group of rheumatoid arthritis patients with a toll-like receptor 4-mediated disease.Arthritis research & therapy · 2016Article
Corrections and comments
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Authors and funding
24 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation is mediated mainly by leukocytes that express both Toll-like receptor 4 (TLR4) and Fc γ receptors (FcγR). Dysregulated activation of leukocytes via exogenous and endogenous ligands of TLR4 results in a large number of inflammatory disorders that underlie a variety of human diseases. Thus, differentially blocking inflammatory cells while sparing structural cells, which are FcγR-negative, represents an elegant strategy when targeting the underlying causes of human diseases. Here, we report a novel tethering mechanism of the Fv and Fc portions of anti-TLR4 blocking antibodies that achieves increased potency on inflammatory cells. In the presence of ligand (e.g. lipopolysaccharide (LPS)), TLR4 traffics into glycolipoprotein microdomains, forming concentrated protein platforms that include FcγRs. This clustering produces a microenvironment allowing anti-TLR4 antibodies to co-engage TLR4 and FcγRs, increasing their avidity and thus substantially increasing their inhibitory potency. Tethering of antibodies to both TLR4 and FcγRs proves valuable in ameliorating inflammation in vivo. This novel mechanism of action therefore has the potential to enable selective intervention of relevant cell types in TLR4-driven diseases.
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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.