AUTHOR=Toscano Alessandro , Elst Jessy , Van Gasse Athina L. , Beyens Michiel , van der Poorten Marie-Line , Bridts Chris H. , Mertens Christel , Van Houdt Michel , Hagendorens Margo M. , Van Remoortel Samuel , Timmermans Jean-Pierre , Ebo Didier G. , Sabato Vito 

TITLE=Mas-related G protein-coupled receptor MRGPRX2 in human basophils: Expression and functional studies

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1026304

DOI=10.3389/fimmu.2022.1026304

ISSN=1664-3224

ABSTRACT=Background: Occupancy of MRGPRX2 heralds a new era in our understandings of immediate drug hypersensitivity reactions (IDHRs), but a constitutive expression of this receptor by basophils is debated. 
Objective: To explore the expression and functionality of MRGPRX2 in and on basophils.
Methods: Basophils from patients with birch pollen allergy, IDHRs to moxifloxacin, and healthy controls were studied in different conditions, that is, in rest, after stimulation with anti-IgE, recombinant major birch pollen allergen (rBet v 1), moxifloxacin, fMLP, substance P (SP), or other potential basophil secretagogues. In a separate set of experiments, basophils were studied after purification and resuspension in different media.
Results: Resting whole blood basophils barely express MRGPRX2 on their surface and are unresponsive to SP or moxifloxacin. However, surface MRGPRX2 is quickly upregulated upon incubation with anti-IgE or fMLP.
Pre-stimulation with anti-IgE can induce a synergic effect on basophil degranulation in IgE-responsive subjects after incubation with SP or moxifloxacin, provided that basophils have been obtained from patients who experienced an IDHR to moxifloxacin.
Cell purification can trigger a “spontaneous” and functional upregulation of MRGPRX2 on basophils, not seen in whole blood cells, and its surface density can be influenced by distinct culture media.
Conclusion: Basophils barely express MRGPRX2 in resting conditions. However, the receptor can be quickly upregulated after stimulation with anti-IgE, fMLP, or after purification, making cells responsive to MRGPRX2 occupation. We anticipate that such “conditioned” basophils constitute a model to explore MRGPRX2 agonism or antagonism, including IDHRs originating from the occupation of this receptor.