Merkel cells as putative new targets of anti-inflammatory drugs

Nicholas Boulais, Ulysse Pereira, Germaine Dorange, Nathalie Rougier, Christophe Chesné, Laurent Misery
University of Western Brittany - Laboratory of Skin Neurobiology, Brest, France

Inflammation is characterized by tissue acidification, cells swelling and histamine release from mast cells. Merkel cells (MC) are epidermal neuroendocrine cells implicated in touch perception and neuropeptides release. Interestingly, they also express the proton-gated osmoreceptor transient receptor potential vanilloid 4 (TRPV4) and the histamine-H3 receptor. We achieved an original culture model wherein enriched porcine Merkel cells were exposed to various substances. We studied the release of vasoactive intestinal peptide (VIP), a neuropeptide with anti-inflammatory properties in the skin. MC from pig snout were retrieved by positive magnetic cells sorting as confirmed by immunocytochemistry and electron microscopy. After 3 days in culture, cells were exposed to histamine, 4αPDD, a phorbol-derivative agonist of TRPV4 and acetylcholine. VIP release was assessed by ELISA. In our culture conditions, MC extended many cytoplasmic processes suggesting a good viability. More than 60% of the cell populations were MC. Following exposure to histamine or the TRPV4 agonist, VIP release was enhanced. Conversely, exposure to acetylcholine led to decreases VIP exocytosis. MC are endowed with ion channels sensitive to inflammation and for which activation enhances VIP release as demonstrated here. Interestingly, VIP is known to down-regulate pro-inflammatory mediators like IL6, IL12, TNFα, inductible nitric oxide synthase and it can up-regulate anti-inflammatory mediators like IL10. Thus, these new findings suggest that MC can take place in regulation of inflammation. The opposite effect of histamine and acetylcholine also argues for a putative role in hypersensitivity and probably atopic dermatitis.