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MRGPRX 2 is negatively targeted by SCF and IL ‐4 to diminish pseudo‐allergic stimulation of skin mast cells in culture
Author(s) -
Babina Magda,
Wang Zhao,
Artuc Metin,
Guhl Sven,
Zuberbier Torsten
Publication year - 2018
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13762
Subject(s) - degranulation , endogeny , stimulation , mast cell , receptor , in vitro , exocytosis , chemistry , allergic response , in vivo , immunology , microbiology and biotechnology , ex vivo , neuroscience , biology , immunoglobulin e , biochemistry , secretion , genetics , antibody
MRGPRX 2 was recently uncovered as the “missing link” in clinically relevant mast cell ( MC ) activation explaining previously puzzling phenomena. It is the receptor for various endogenous ligands and exogenous compounds alike, whose binding evokes rapid degranulation much like allergen‐mediated exocytosis. While the perceivable outcomes are similar, the two activation routes differ regarding mechanism and regulation. We recently reported that acute SCF administration curbs responses evoked by MRGPRX 2 in human skin MC s. Maintenance of MC s in culture requires the presence of MC supportive factors and renders the cells functionally and molecularly unequal to ex vivo counterparts. Here, we asked whether expansion in culture impacts the pseudo‐allergic route, and if so, what contribution SCF and IL ‐4 play in this scenario. We report that the in vitro micromilieu dampens (but does not erase) pseudo‐allergic responses and that this is accompanied by strongly reduced MRGPRX 2 expression. Withdrawal of SCF or IL ‐4 individually, but most potently of both collectively, partially reinstates the MRGPRX 2 pathway, revealing that SCF and IL ‐4 make negative adjustments to the pseudo‐allergic pathway. Under all conditions, the Fcε RI ‐triggered route showed the inverse pattern of regulation, substantiating that allergic and pseudo‐allergic MC activation can obey opposite rules, hinting at possible competition between them.