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Recently, however, MCs have been demonstrated to be also thermo\u2010sensitive, suggesting that their role in skin physiologically extends well beyond mechanosensation. Here, we demonstrate that in healthy human skin epidermal MCs express functional olfactory receptors, namely OR2AT4, just like neighbouring keratinocytes. Selective stimulation of OR2AT4 by topical application of the synthetic odorant, Sandalore\u00ae, significantly increased Piccolo protein expression in MCs, as assessed by quantitative immunohistomorphometry, indicating increased vesicle trafficking and recycling, and significantly reduced nerve growth factor (NGF) immunoreactivity within MCs, possibly indicating increased neurotrophin release upon OR2AT4 activation. Live\u2010cell imaging showed that Sandalore\u00ae rapidly induces a loss of FFN206\u2010dependent fluorescence in MCs, suggesting OR2AT4\u2010dependent MC depolarization and subsequent vesicle secretion. Yet, in contrast to keratinocytes, OR2AT4 stimulation by Sandalore\u00ae altered neither the number nor the proliferation status of MCs. These preliminary ex vivo findings demonstrate that epidermal MCs also exert OR\u2010dependent chemosensory functions in human skin, and invite one to explore whether these newly identified properties are dysregulated in selected skin disorders, for example, in pruritic dermatoses, and if these novel MC functions can be therapeutically targeted to maintain\/promote skin health.<\/jats:p>","DOI":"10.1111\/exd.14907","type":"journal-article","created":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T21:35:18Z","timestamp":1692567318000},"page":"1848-1855","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Preliminary evidence that Merkel cells exert chemosensory functions in human epidermis"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-895X","authenticated-orcid":false,"given":"Ilaria","family":"Piccini","sequence":"first","affiliation":[{"name":"Monasterium Laboratory Skin and Hair Research Solutions GmbH  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1901-0551","authenticated-orcid":false,"given":"Jeremy","family":"Ch\u00e9ret","sequence":"additional","affiliation":[{"name":"Monasterium Laboratory Skin and Hair Research Solutions GmbH  M\u00fcnster Germany"},{"name":"Dr. Phillip Frost Department of Dermatology\u00a0&amp; Cutaneous Surgery University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9953-7219","authenticated-orcid":false,"given":"Moe","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"MIRAI Technology Institute Shiseido Co., Ltd.  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