{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:19:58Z","timestamp":1747181998457,"version":"3.40.5"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diphencyprone (DPCP) is a hapten that causes a delayed\u2010type hypersensitivity reaction when applied topically. It has clinical uses in the treatment of various conditions such as melanoma metastases, warts, and alopecia areata, but the mechanisms are currently not well understood in humans. To further characterize the immunologic effects of DPCP, the authors performed a proteomic analysis of normal skin of eight healthy volunteers following a single application of DPCP and compared them with placebo\u2010treated skin from the same volunteers. A total of 96 proteins were examined using the Olink immuno\u2010oncology panel at 3\u2009days (peak response), 14\u2009days (partially resolved response), and 120\u2009days (completely resolved response). Our analysis revealed significant upregulation of markers of immune cell activation (interleukin [IL] 8), vascular and tissue remodeling (matrix metallopeptidase 12 [MMP12], nitric oxide synthase 3 [NOS3]), antineoplastic markers (granzyme B [GZMB]), and the Th1 axis (interferon gamma [IFNG], chemokine (C\u2010X\u2010C motif) ligand [CXCL] 9, CXCL10, CXCL11) at days 3 and 14 compared with placebo (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In addition, several negative regulators of immune function such as programmed cell death 1 (PD1), programmed cell death ligand 1 (PDL1) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and lymphocyte activation gene 3 (LAG3) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) were significantly upregulated at days 3 and 14. This induction of negative regulators may explain the seemingly paradoxical therapeutic benefits of DPCP in autoimmune conditions such as alopecia areata. The current analysis also indicated IL\u20104 upregulation only at day 3, followed by IL\u201012 upregulation only at day 14, suggesting a transient Th2 response followed by Th1 polarization. Overall, these data suggest a complex and evolving immunological delayed\u2010type hypersensitivity response to a single application of DPCP over time. Future proteomic studies of samples from patients with melanoma metastases, warts, and alopecia areata treated long term with DPCP are needed to further evaluate its pharmacologic mechanisms.<\/jats:p>","DOI":"10.1111\/1346-8138.16688","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T04:58:55Z","timestamp":1672289935000},"page":"804-809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unique protein signatures evolve during the course of a delayed\u2010type hypersensitivity reaction in human skin"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-6926","authenticated-orcid":false,"given":"Joseph","family":"Han","sequence":"first","affiliation":[{"name":"Department of Dermatology Icahn School of Medicine at Mount Sinai  New York New York 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