ArticleFrontiers in immunology2024
Neuronal substance P-driven MRGPRX2-dependent mast cell degranulation products differentially promote vascular permeability.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Targeting the neuro-immune-skin axis: Advanced functional biomaterials for intelligent wound management and regeneration.Materials today. Bio · 2026Review
- Developments in Mast Cell Research.The Journal of allergy and clinical immunology · 2026Review
- The Mast Cell-Substance P Neuroimmune Axis in Allergic Contact Dermatitis and Atopic Dermatitis: Molecular Mechanisms and Pathophysiological Perspectives.Current issues in molecular biology · 2026Review
- Immunopathogenesis of itch: an integrative framework for chronic pruritus.JID innovations : skin science from molecules to population health · 2026Review
- Neuroimmune Regulation in Posttraumatic Bone Repair: From Inflammatory Transition to Neurovascular Coupling and Functional Recovery.Journal of cellular physiology · 2026Review
- The SP-MrgprX2 Axis in Allergic Rhinitis: a Neuro-immune Paradigm Beyond IgE-mediated Inflammation.Clinical reviews in allergy & immunology · 2026Review
- Broadening the View: Substance P and Its Metabolism in Pruritus-Related Diseases.The Journal of dermatology · 2026Review
- Aeroallergens in Atopic Dermatitis and Chronic Urticaria.Current allergy and asthma reports · 2026Review
- Three-dimensional modeling of sensory nerve architecture and eosinophil and mast cell interactions in eosinophilic gastrointestinal disease.Journal of leukocyte biology · 2026Article
- Review
- Exploring the Role of Gut Microbiota in Chronic Spontaneous Urticaria: Mechanisms and Potential Therapeutic Implications.Probiotics and antimicrobial proteins · 2026Review
- The Connections Between Pain and Itch: Shared Neuroimmune Mechanisms and Therapeutic Implications.Current pain and headache reports · 2026Review
- Mast Cells and Substance P: Neuroinflammatory Loops at the Molecular and Translational Clinical Levels.Biomolecules · 2026Review
- Role of Mast Cells and Neuroinflammation in Neuropsychiatric Disorders of the Developmental Period.Biomolecules · 2026Review
- MRGPRX2 as a novel therapeutic target in headache.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Keratinocytes: pleiotropic orchestrators of cutaneous immunity and Inflammation - Emerging therapeutic paradigms in dermatological pathologies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- From skin to lung: basophil-mediated spread of allergic diseases.Frontiers in immunology · 2026Review
- The neuroimmune axis in cardiovascular disease: from immune activation to inflammatory resolution.Frontiers in immunology · 2026Review
- Neuro-immune-vascular interactions in rosacea and hypertension: a mechanistic review.Frontiers in immunology · 2026Review
- Neuro-immune interactions in urticaria:a pruritus-centric dissection.Frontiers in immunology · 2026Review
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Authors and funding
17 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Mas-related G protein-coupled receptor b2 (Mrgprb2) binding to its cationic endogenous and exogenous ligands induces mast cell degranulation and promotes inflammation in mice. However, the physiological roles of its human homologue MRGPRX2 remain unclear. Here we aimed to elucidate the mechanisms by which MRGPRX2 regulates vascular permeability, and generated MRGPRX2 knock-in (MRGPRX2-KI) and Mrgprb2 knockout (Mrgprb2-KO) mice. Substance P (SP) and ciprofloxacin strongly degranulated MRGPRX2-KI peritoneal mast cells (PMCs) better than WT PMCs, whereas Dermatophagoides pteronyssinus (Der p) extract and phenol-soluble modulin α3 (PSMα3) did not degranulate PMCs. SP-stimulated MRGPRX2-KI PMCs released large amounts of histamine and mast cell protease 4 (MCPT4) chymase. Der p extract, PSMα3, and MCPT4, but not histamine, induced SP release from dorsal root ganglion (DRG) cells. However, this effect of Der p extract/PSMα3 was suppressed by a transient receptor potential vanilloid 1 (TRPV1) antagonist. SP-, ciprofloxacin-, Der p extract-, PSMα3-, and MCPT4-induced vascular permeability was highest in MRGPRX2-KI mice, which depended on SP. In addition, SP-, ciprofloxacin- and PSMα3-induced MRGPRX2-dependent vascular hyperpermeability was suppressed by antihistamine and chymase inhibitor. TRPV1 antagonist also inhibited PSMα3-induced MRGPRX2-dependent vascular hyperpermeability. Both Mrgprb2-KO and MRGPRX2-KI did not influence the histamine-induced murine vascular hyperpermeability. Overall, our results suggest that neuronal SP induces MRGPRX2-dependent mast cell degranulation, releasing histamine and chymase, which promote vascular hyperpermeability directly or indirectly via DRG cell activation. Importantly, the worsening cycle (MRGPRX2 → mast cell degranulation → chymase → DRG activation → SP → MRGPRX2) seems to play an important role in human MRGPRX2-depdendent inflammation.
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