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Int. J. Mol. Sci. 2017, 18(3), 525; doi:10.3390/ijms18030525

Retinoic Acid Negatively Impacts Proliferation and MCTC Specific Attributes of Human Skin Derived Mast Cells, but Reinforces Allergic Stimulability

Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany
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Author to whom correspondence should be addressed.
Academic Editor: Ge Zhang
Received: 16 November 2016 / Revised: 20 February 2017 / Accepted: 21 February 2017 / Published: 28 February 2017
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
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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. View Full-Text
Keywords: mast cell; retinoic acid; skin; proliferation; cell cycle; IgER; tryptase; chymase mast cell; retinoic acid; skin; proliferation; cell cycle; IgER; tryptase; chymase
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MDPI and ACS Style

Babina, M.; Artuc, M.; Guhl, S.; Zuberbier, T. Retinoic Acid Negatively Impacts Proliferation and MCTC Specific Attributes of Human Skin Derived Mast Cells, but Reinforces Allergic Stimulability. Int. J. Mol. Sci. 2017, 18, 525.

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