Retinoic acid potentiates inflammatory cytokines in human mast cells: identification of mast cells as prominent constituents of the skin retinoid network

Molecular and Cellular Endocrinology
Magda BabinaTorsten Zuberbier

Abstract

Retinoic acid (RA), the active vitamin-A-metabolite, has well-established functions in skin homeostasis and in the immune system. Skin mast cells (MCs) combine traits of both structures, being of hematopoietic origin, but functional in the skin environment. It remains largely unknown whether mature MCs are targeted by the retinoid network. Here, we demonstrate that human skin MCs display substantial susceptibility to RA by which they are instructed to increase pro-inflammatory mediators (IL-1β, IL-8, TNF-α) but not histamine release. The effects are observed at physiological RA levels, in different microenvironments, and are largely donor-independent. RA susceptibility is owed to the cells' abundant expression of RARA, the receptor mediating MC cytokine responses. Unexpectedly, bioinformatics calculations on the FANTOM5 expression atlas revealed general enrichment of retinoid network components in MCs against other skin cells, and MCs rapidly upregulated RA responsive genes. In conclusion, MCs are important yet hitherto overlooked retinoid targets in the skin.

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Citations

Apr 19, 2017·Experimental Dermatology·Tarek HazzanMagda Babina
Aug 20, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marc C LigginsRichard L Gallo
Jan 6, 2019·International Journal of Environmental Research and Public Health·Anthony R Mawson, Ashley M Croft
Sep 26, 2020·Frontiers in Pharmacology·Astrid HogenkampLinette E M Willemsen
Dec 29, 2015·Experimental Dermatology·Magda BabinaTorsten Zuberbier
Aug 31, 2017·Scientific Reports·Aswin HariHsiao-Huei Chen
Aug 17, 2018·Case Reports in Dermatological Medicine·Amal A Kokandi
May 1, 2021·International Journal of Molecular Sciences·Paola Leonor QuanGabriel Gastaminza

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