{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:27:34Z","timestamp":1789694854550,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003958","name":"Stichting voor de Technische Wetenschappen","doi-asserted-by":"publisher","award":["13382"],"award-info":[{"award-number":["13382"]}],"id":[{"id":"10.13039\/501100003958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Contact Dermatitis"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The nature of clinically related adverse reactions to titanium is still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether titanium salts have irritant or sensitizing potential in a reconstructed human skin (RHS) model with integrated Langerhans cells (LCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RHS\u2010LCs (ie, reconstructed epidermis) containing primary differentiated keratinocytes and CFSE<jats:sup>+<\/jats:sup>CD1a<jats:sup>+<\/jats:sup>\u2010LCs generated from the MUTZ\u20103 cell line on a primary fibroblast\u2010populated collagen hydrogel (dermis) were topically exposed to titanium(IV) bis(ammonium lactato)dihydroxide (TiALH). LC migration and plasticity were determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TiALH resulted in CFSE<jats:sup>+<\/jats:sup>CD1a<jats:sup>+<\/jats:sup>\u2010LC migration out of the epidermis. Neutralizing antibodies to CCL5 and CXCL12 showed that LC migration was CCL5 and not CXCL12 mediated. LCs accumulating within the dermis after TiALH exposure were CFSE<jats:sup>+<\/jats:sup>Lang<jats:sup>+<\/jats:sup>CD68<jats:sup>+<\/jats:sup> which is characteristic of a phenotypic switch of MUTZ\u2010LC to a macrophage\u2010like cell. Furthermore, TiALH did not result in increased interleukin (IL)\u20101\u03b2 or CCR7 messenger RNA (mRNA) in the dermis, but did result in increased IL\u201010 mRNA. In addition, monocultures of MUTZ\u2010LCs failed to increase LC maturation biomarkers CD83, CD86, and CXCL\u20108 when exposed to noncytotoxic concentrations of four different titanium salts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results classify titanium salts as irritants rather than sensitizers and indicate that titanium implant\u2010related complaints could be due to localized irritant\u2010mediated inflammation arising from leachable agents rather than a titanium metal allergy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cod.13666","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T05:36:24Z","timestamp":1594964184000},"page":"337-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Titanium salts tested in reconstructed human skin with integrated <scp>MUTZ<\/scp>\u20103\u2010derived Langerhans cells show an irritant rather than a sensitizing potential"],"prefix":"10.1111","volume":"83","author":[{"given":"Charlotte T.","family":"Rodrigues Neves","sequence":"first","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander W.","family":"Spiekstra","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels P. 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