ArticleGastroenterology2021
Inflamed Ulcerative Colitis Regions Associated With MRGPRX2-Mediated Mast Cell Degranulation and Cell Activation Modules, Defining a New Therapeutic Target.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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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.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Understanding heterogeneity in the pathogenesis and drug responses of ulcerative colitis through single-cell and spatial transcriptomics.Frontiers in immunology · 2026Pooled it
- Article
- Inflammatory and Immune Cytoprofiles of Active Ulcerative Colitis from Crohn's Disease-Insights from Multivariable Modeling.International journal of molecular sciences · 2026Article
- Use of Antihistamine Drugs in Colitis: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Mast Cells and Substance P: Neuroinflammatory Loops at the Molecular and Translational Clinical Levels.Biomolecules · 2026Review
- Loss of E3 ligase Ube4A Disrupts Colon Homeostasis and Accelerates Experimental Colitis via Altered Lipid Handling.bioRxiv : the preprint server for biology · 2026Article
- Regulation of MRGPRX2-mediated mast cell function by competence-stimulating peptide 1 and pro-adrenomedullin peptide.Frontiers in immunology · 2026Article
- Neuro-immune-epithelial pathways involving substance P may contribute to mucosal pathology in gastro-oesophageal reflux disease.Frontiers in immunology · 2026Article
- Hereditary α-tryptasemia; a review of mechanisms linking α-tryptase gene dosage to intestinal homeostasis and immunopathology.Frontiers in allergy · 2026Review
- Effect of Electroacupuncture on Intestinal Mucosal Barrier in IBS-D Rats: Analysis Based on RNA-seq.Combinatorial chemistry & high throughput screening · 2026Article
- Mast Cells Inhibit Stem Cell-driven Epithelial Repair in Inflammatory Bowel Disease via Suppressing Wnt/lrp6/β-Catenin Signaling Pathway.Cellular and molecular gastroenterology and hepatology · 2026Article
- 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
- Mutations ofThe journal of allergy and clinical immunology. Global · 2025Review
- MRGPRX2 Mediates Mast Cell-Induced Endometriosis Pain Through the Sensitization of Sensory Neurons via Histamine/HRH1/TRPV1 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Aberrant Activation of Mast Cells: Molecular Mechanisms and Targets for Intervention.Clinical reviews in allergy & immunology · 2025Review
- The PAD4 inhibitor GSK484 diminishes neutrophil extracellular trap in the colon mucosa but fails to improve inflammatory biomarkers in experimental colitis.Bioscience reports · 2025Article
- Antimicrobial Peptide Signaling in Skin Diseases.JID innovations : skin science from molecules to population health · 2025Review
- Beyond the classic players: Mas-related G protein-coupled receptor member X2 role in pruritus and skin diseases.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Review
- Beyond the "Master" Role in Allergy: Insights into Intestinal Mast Cell Plasticity and Gastrointestinal Diseases.Biomedicines · 2025Review
- Eleven Grand Challenges for Inflammatory Bowel Disease Genetics and Genomics.Inflammatory bowel diseases · 2025Review
Corrections and comments
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Authors and funding
28 authors at 8 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsRecent literature has implicated a key role for mast cells in murine models of colonic inflammation, but their role in human ulcerative colitis (UC) is not well established. A major advance has been the identification of mrgprb2 (human orthologue, MRGPX2) as mediating IgE-independent mast cell activation. We sought to define mechanisms of mast cell activation and MRGPRX2 in human UC.
methodsColon tissues were collected from patients with UC for bulk RNA sequencing and lamina propria cells were isolated for MRGPRX2 activation studies and single-cell RNA sequencing. Genetic association of all protein-altering G-protein coupled receptor single-nucleotide polymorphism was performed in an Ashkenazi Jewish UC case-control cohort. Variants of MRGPRX2 were transfected into Chinese hamster ovary (CHO) and human mast cell (HMC) 1.1 cells to detect genotype-dependent effects on β-arrestin recruitment, IP-1 accumulation, and phosphorylated extracellular signal-regulated kinase.
resultsMast cell-specific mediators and adrenomedullin (proteolytic precursor of PAMP-12, an MRGPRX2 agonist) are up-regulated in inflamed compared to uninflamed UC. MRGPRX2 stimulation induces carboxypeptidase secretion from inflamed UC. Of all protein-altering GPCR alleles, a unique variant of MRGPRX2, Asn62Ser, was most associated with and was bioinformatically predicted to alter arrestin recruitment. We validated that the UC protective serine allele enhances β-arrestin recruitment, decreases IP-1, and increases phosphorylated extracellular signal-regulated kinase with MRGPRX2 agonists. Single-cell RNA sequencing defines that adrenomedullin is expressed by activated fibroblasts and epithelial cells and that interferon gamma is a key upstream regulator of mast cell gene expression.
conclusionInflamed UC regions are distinguished by MRGPRX2-mediated activation of mast cells, with decreased activation observed with a UC-protective genetic variant. These results define cell modules of UC activation and a new therapeutic target.
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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.