All-trans retinoic acid activated mast cells via Mas-related G protein coupled receptor-X2 in retinoid dermatitis.

BACKGROUND: Retinoic acid (RA) induced dermatitis is the most frequent side effect which limits its wide use. However, the exact mechanisms triggering dermatitis is not fully understood, including the role of skin mast cells. The newly discovered MRGPRX2 in mast cells mediates pseudoallergic drug reactions in several types of dermatitis. A possible contribution of MRGPRX2 to contact dermatitis induced by RA has hitherto not been examined.

OBJECTIVES: To investigate whether all-trans retinoic acid (ATRA) activates mast cells via MRGPRX2/MrgprB2(the mouse ortholog), which contribute to pathogenesis of retinoid-induced dermatitis.

METHODS: Wild-type (WT) and MrgprB2-/- mice were treated with topical ATRA to observe local inflammation and mast cell degranulation in vivo by Haematoxilin & Eosin and immunofluorescence staining. Release of histamine and β-hexosaminidase were measured and calcium influx were detected in LAD2 cells with specific knockdown targeting MRGPRX2 by siRNA and primary cells from MrgprB2-/- mice.

RESULTS: Compared to WT mice, MrgprB2-/- mice showed resistance to ATRA triggered contact dermatitis and local inflammatory reactions in paws. ATRA activated mast cells via MrgprB2 pathway in murine, and via MRGPRX2 pathway in human mast cells.

CONCLUSIONS: ATRA induced dermatitis could be achieved by activating mast cells via MRGPRX2/MrgprB2， which may provide the potential therapy target to reduce the side effect. This article is protected by copyright. All rights reserved.