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• W2593598034 abstract "The Vitamin-A-metabolite retinoic acid (RA) acts as a master regulator of cellular programs. Mast cells (MCs) are primary effector cells of type-I-allergic reactions. We recently uncovered that human cutaneous MCs are enriched with RA network components over other skin cells. Yet, direct experimental evidence on the significance of the RA-MC axis is limited. Here, skin-derived cultured MCs were exposed to RA for seven days and investigated by flow-cytometry (BrdU incorporation, Annexin/PI, FcεRI), microscopy, RT-qPCR, histamine quantitation, protease activity, and degranulation assays. We found that while MC size and granularity remained unchanged, RA potently interfered with MC proliferation. Conversely, a modest survival-promoting effect from RA was noted. The granule constituents, histamine and tryptase, remained unaffected, while RA had a striking impact on MC chymase, whose expression dropped by gene and by peptidase activity. The newly uncovered MRGPRX2 performed similarly to chymase. Intriguingly, RA fostered allergic MC degranulation, in a way completely uncoupled from FcεRI expression, but it simultaneously restricted MRGPRX2-triggered histamine release in agreement with the reduced receptor expression. Vitamin-A-derived hormones thus re-shape skin-derived MCs numerically, phenotypically, and functionally. A general theme emerges, implying RA to skew MCs towards processes associated with (allergic) inflammation, while driving them away from the skin-imprinted MCTC (MCs containing tryptase and chymase) signature (chymase, MRGPRX2). Collectively, MCs are substantial targets of the skin retinoid network." @default.
• W2593598034 created "2017-03-16" @default.
• W2593598034 creator A5004878337 @default.
• W2593598034 creator A5008487990 @default.
• W2593598034 creator A5013934017 @default.
• W2593598034 creator A5015855045 @default.
• W2593598034 date "2017-02-28" @default.
• W2593598034 modified "2023-10-01" @default.
• W2593598034 title "Retinoic Acid Negatively Impacts Proliferation and MCTC Specific Attributes of Human Skin Derived Mast Cells, but Reinforces Allergic Stimulability" @default.
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• W2593598034 doi "https://doi.org/10.3390/ijms18030525" @default.
• W2593598034 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5372541" @default.
• W2593598034 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28264498" @default.
• W2593598034 hasPublicationYear "2017" @default.
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