ArticleFrontiers in immunology2022
The Inhibitory Receptor Siglec-8 Interacts With FcεRI and Globally Inhibits Intracellular Signaling in Primary Mast Cells Upon Activation.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Mast cell proteases and their significance in physiology, pathology, and therapeutic approaches.Pharmacological reviews · 2026Review
- Neuroimmune Regulation of Microvascular Inflammation: The Heart-Brain Axis, Mast Cells, and the Protective Role of Flavonoids-A Comprehensive Review.Biomedicines · 2026Review
- Nanomaterials in Targeted Immunotherapy for Chronic Spontaneous Urticaria: Focusing on Immune Cell Modulation and Precision Treatment.International journal of nanomedicine · 2026Review
- MRGPRX2-expressing mast cells are increased in the GI tract of individuals with active inflammatory bowel disease and hereditary α-tryptasemia.medRxiv : the preprint server for health sciences · 2025Article
- Identification and Validation of Differentially Expressed mRNAs From Peripheral Leukocytes for Acute Stanford Type A Aortic Dissection.Journal of the American Heart Association · 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
- Advances and Challenges in the Development of New and Novel Treatment Strategies for Eosinophilic Esophagitis (EoE).Pharmaceuticals (Basel, Switzerland) · 2025Review
- Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer.International journal of molecular sciences · 2025Review
- Mast cell-neuron axis as a core mechanism in chronic pruritus of atopic dermatitis: from mechanistic insights to therapeutic targets.Frontiers in immunology · 2025Review
- Caffeine Acts as an Agonist of Siglec-6, Inhibits MRGPRX2-Triggered Mast Cell Degranulation and Anaphylactoid Reactions.Mediators of inflammation · 2025Article
- MRGPRX2-expressing mast cells are increased in the GI tract of individuals with active inflammatory bowel disease and hereditary α-tryptasemia.Frontiers in allergy · 2025Article
- Dissecting the Ability of Siglecs To Antagonize Fcγ Receptors.ACS central science · 2024Article
- Gut microbiota facilitate chronic spontaneous urticaria.Nature communications · 2024Article
- Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases.Seminars in immunology · 2023Review
- Recent Advances in the Treatment of Eosinophilic Esophagitis.The journal of allergy and clinical immunology. In practice · 2023Review
- Discovery, classification, evolution and diversity of Siglecs.Molecular aspects of medicine · 2023Review
- Siglecs in allergy and asthma.Molecular aspects of medicine · 2023Review
- Drug delivery targets and strategies to address mast cell diseases.Expert opinion on drug delivery · 2023Review
- Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody.JACS Au · 2023Article
- Interactions between Siglec-8 and endogenous sialylated cis ligands restrain cell death induction in human eosinophils and mast cells.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunomodulation of mast cell (MC) activity is warranted in allergic and inflammatory diseases where MCs have a central role in pathogenesis. Targeting Siglec-8, an inhibitory receptor on MCs and eosinophils, has shown promising activity in preclinical and clinical studies. While the intracellular pathways that regulate Siglec-8 activity in eosinophils have been well studied, the signaling mechanisms that lead to MC inhibition have not been fully elucidated. Here, we evaluate the intracellular signaling pathways of Siglec-8-mediated inhibition in primary MCs using an anti-Siglec-8 monoclonal antibody (mAb). Phospho-proteomic profiling of FcεRI-activated MCs revealed Siglec-8 mAb-treatment globally inhibited proximal and downstream kinases, leading to attenuated MC activation and degranulation. In fact, Siglec-8 was found to directly interact with FcεRI signaling molecules. Siglec-8 inhibition was dependent on both cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that interact with the SH2 containing protein phosphatase Shp-2 upon Siglec-8 phosphorylation. Taken together, these data support a model in which Siglec-8 regulates proximal FcεRI-induced phosphorylation events through phosphatase recruitment and interaction with FcεRIγ, resulting in global inhibition of MCs upon Siglec-8 mAb engagement.
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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.