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Review
. 2024 Nov 25;25(1):5.
doi: 10.1007/s11882-024-01183-5.

Mast Cells and Mas-related G Protein-coupled Receptor X2: Itching for Novel Pathophysiological Insights to Clinical Relevance

Mariana Castells  1 , Michael Madden  2 , Carole A Oskeritzian  3
Affiliations
Review

Mast Cells and Mas-related G Protein-coupled Receptor X2: Itching for Novel Pathophysiological Insights to Clinical Relevance

Mariana Castells et al. Curr Allergy Asthma Rep. .

Abstract

Purpose of review: Clinical interest in non-IgE activation of mast cells has been growing since the description of the human MRGPRX2 receptor. Its participation in many allergic and inflammatory conditions such as non histaminergic itch, urticaria, asthma and drug hypersensitivity has been growing. We present here an updated review of its structure, expression and biology to help understand conditions and diseases attributed to its activation and/or overpexression and the search for agonists and antagonists of clinical utility.

Recent findings: The description of patients presenting anaphylaxis when exposed to one or multiple MRGPRX2 agonists such as general anesthetics, antibiotics, opiods and other agents has provided evidence of potential heterogeneity in humans. This review provides the most recent developments into the receptor structure, tissue expression and signaling pathways including the potential enhancement of IgE-mediated mast cell activation. New insight into its agonists and antagonists is described and future developments to adress its modulations.

Keywords: Allergy; Drug hypersensitivity; FceRI; MRGPRX2; Mast cell; Non-IgE.

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Conflict of interest statement

Declarations. Competing Interests: Mariana Castells is Editor in Chief and did not play any part in the assignment of this manuscript to Associate Editors or peer reviewers and is separated and blinded from the editorial system from submission inception to decision. Carole Oskeritzian has grant funding from The National Institutes of Health/National Institute for General Medical Sciences. Carole Oskeritzian has grant funding from The National Institutes of Health/National Institute for General Medical Sciences. Michael Madden declares that he has no conflict of interest. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors.

Figures

Fig. 1
Fig. 1
Snake diagram of MRGPRX2 (a). Sex-specific bulk tissue-level gene expression of MRGPRX2 (gtexportal.org/home/gene/ENSG00000183695) (b)
Fig. 2
Fig. 2
Comparison of MRGPRX2 and FCεR1/IgE signaling pathways
Fig. 3
Fig. 3
MRGPRX2 Agonists and Antagonists (a, c). THIQ motif identified in several MRGPRX2- activating drugs (b)
See this image and copyright information in PMC

References

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