{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:34:32Z","timestamp":1792467272577,"version":"4.5.0"},"reference-count":82,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor\u2019s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48\/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.<\/jats:p>","DOI":"10.3390\/ijms22094421","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T12:08:30Z","timestamp":1619179710000},"page":"4421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1542-1919","authenticated-orcid":false,"given":"Paola Leonor","family":"Quan","sequence":"first","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2200-0485","authenticated-orcid":false,"given":"Marina","family":"Sabat\u00e9-Bresc\u00f3","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Health Research Institute (Instituto de Investigaci\u00f3n Sanitaria de Navarra) (IdiSNA), 31008 Navarra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Guo","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Biomedicine Department, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Laboratory of Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Biomedicine Department, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Laboratory of Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6325-3847","authenticated-orcid":false,"given":"Gabriel","family":"Gastaminza","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Health Research Institute (Instituto de Investigaci\u00f3n Sanitaria de Navarra) (IdiSNA), 31008 Navarra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S0092-8674(01)00483-4","article-title":"A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons","volume":"106","author":"Dong","year":"2001","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.jaci.2016.04.051","article-title":"Roles of Mas-related G protein\u2013coupled receptor X2 on mast cell\u2013mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases","volume":"138","author":"Subramanian","year":"2016","journal-title":"J. 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