ArticleCommunications biology2022
Discovery of an agonistic Siglec-6 antibody that inhibits and reduces human mast cells.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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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
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Sequence variant affects GCSAML splicing, mast cell specific proteins, and risk of urticaria.Communications biology · 2023Pooled it
- Selective elimination of mast cells via Siglec-6-targeted nanodelivery of drug payload.The Journal of allergy and clinical immunology · 2026Article
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Advances in the Management of Mediator-Related Symptoms in Non-Advanced Systemic Mastocytosis.ImmunoTargets and therapy · 2026Review
- Caffeine Acts as an Agonist of Siglec-6, Inhibits MRGPRX2-Triggered Mast Cell Degranulation and Anaphylactoid Reactions.Mediators of inflammation · 2025Article
- Therapeutic monoclonal antibodies in allergy: Targeting IgE, cytokine, and alarmin pathways.Immunological reviews · 2024Review
- Controlled adsorption of multiple bioactive proteins enables targeted mast cell nanotherapy.Nature nanotechnology · 2024Article
- Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases.Seminars in immunology · 2023Review
- Research Advances in Mast Cell Biology and Their Translation Into Novel Therapies for Anaphylaxis.The journal of allergy and clinical immunology. In practice · 2023Review
- A mast cell-related prognostic model for non-small cell lung cancer.Journal of thoracic disease · 2023Article
- Immunologic, genetic, and ecological interplay of factors involved in allergic diseases.Frontiers in allergy · 2023Review
- Chronic spontaneous urticaria: update on pathogenesis and therapeutic implications.Anais brasileiros de dermatologiaReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mast cells (MC) are key drivers of allergic and inflammatory diseases. Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 is an immunoregulatory receptor found on MCs. While it is recognized that engaging Siglecs with antibodies mediates inhibition across immune cells, the mechanisms that govern this agonism are not understood. Here we generated Siglec-6 mAb clones (AK01 to AK18) to better understand Siglec-6-mediated agonism. Siglec-6 mAbs displayed epitope-dependent receptor internalization and inhibitory activity. We identified a Siglec-6 mAb (AK04) that required Fc-mediated interaction for receptor internalization and induced inhibition and antibody-dependent cellular phagocytosis against MCs. AK04-mediated MC inhibition required Siglec-6 immunoreceptor tyrosine-based inhibitory motif (ITIM) and ITIM-like domains and was associated with receptor cluster formation containing inhibitory phosphatases. Treatment of humanized mice with AK04 inhibited systemic anaphylaxis with a single dose and reduced MCs with chronic dosing. Our findings suggest Siglec-6 activity is epitope dependent and highlight an agonistic Siglec-6 mAb as a potential therapeutic approach in allergic disease.
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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.