{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:02:03Z","timestamp":1779163323507,"version":"3.51.4"},"reference-count":10,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T00:00:00Z","timestamp":1433980800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Diphencyprone (DPCP) is a hapten that causes delayed-type hypersensitivity (DTH) reactions in human skin, and is used as a topical therapeutic for alopecia areata, warts, and cutaneous melanoma metastases.\u00a0 We examined peak DTH reactions induced by DPCP (3 days post-challenge) by comprehensive gene expression and histological analysis.\u00a0 To better understand how these DTH reactions naturally resolve, we compared our DPCP biopsies to those from patients with psoriasis vulgaris, a chronic inflammatory disease that does not resolve.\u00a0 By both microarray and qRT-PCR, we found that psoriasis lesional skin has significantly lower expression of many negative immune regulators compared to peak DPCP reactions.\u00a0 These regulators include: interleukin-10, cytotoxic T lymphocyte-associated 4 (CTLA4), programmed cell death 1 (PD1), programmed cell death 1 ligand 1 (PDL1), programmed cell death 1 ligand 2 (PDL2), and indoleamine 2,3-dioxygenase (IDO1).\u00a0 Their decreased expression was confirmed at the protein level by immunohistochemistry.\u00a0 To more completely determine the balance of positive vs. negative immune regulators in both DPCP reactions and psoriasis, we developed one comprehensive gene list for positive regulatory (inflammatory) genes, and another for negative regulatory (immunosuppressive) genes, through Gene Ontology terms and literature review.\u00a0 With this approach, we found that DPCP reactions have a higher ratio of negative to positive regulatory genes (both in terms of quantity and expression levels) than psoriasis lesional skin.\u00a0 These data suggest that the disease chronicity that distinguishes psoriasis from transient DTH reactions may be related to absence of negative immune regulatory pathways, and induction of these is therefore of therapeutic interest.\u00a0 Further study of these negative regulatory mechanisms that are present in DPCP reactions, but not in psoriasis, could reveal novel players in the pathogenesis of chronic inflammation.\u00a0 The DPCP system used here thus provides a tractable model for primary discovery of pathways potentially involved in immune regulation in peripheral tissues.<\/ns4:p>","DOI":"10.12688\/f1000research.6581.1","type":"journal-article","created":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T05:40:06Z","timestamp":1434001206000},"page":"149","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Psoriasis is characterized by deficient negative immune regulation compared to transient delayed-type hypersensitivity reactions"],"prefix":"10.12688","volume":"4","author":[{"given":"Nicholas","family":"Gulati","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayte","family":"Su\u00e1rez-Fari\u00f1as","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Correa da Rosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James G.","family":"Krueger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2015,6,11]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"12-7","DOI":"10.1046\/j.1523-1747.2003.12165.x","article-title":"Alopecia areata: treatment of today and tomorrow.","volume":"8","author":"P Freyschmidt-Paul","year":"2003","journal-title":"J Investig Dermatol Symp Proc."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"214-7","DOI":"10.1007\/s10227-001-0050-9","article-title":"The use of diphenylcyclopropenone in the treatment of recalcitrant warts.","volume":"6","author":"J Upitis","year":"2002","journal-title":"J Cutan Med Surg."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"308-13","DOI":"10.1002\/jso.23506","article-title":"Topical immunotherapy with diphencyprone for in transit and cutaneously metastatic melanoma.","volume":"109","author":"D Damian","year":"2014","journal-title":"J Surg Oncol."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"530-3","DOI":"10.1111\/1523-1747.ep12395722","article-title":"Cytokine mRNA levels in Alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone.","volume":"103","author":"R Hoffmann","year":"1994","journal-title":"J Invest Dermatol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"2531-40","DOI":"10.1038\/jid.2014.196","article-title":"Molecular characterization of human skin response to diphencyprone at peak and resolution phases: therapeutic insights.","volume":"134","author":"N Gulati","year":"2014","journal-title":"J Invest Dermatol."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"e44274","DOI":"10.1371\/journal.pone.0044274","article-title":"Meta-analysis derived (MAD) transcriptome of psoriasis defines the \u201ccore\u201d pathogenesis of disease.","volume":"7","author":"S Tian","year":"2012","journal-title":"PLoS One."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/1471-2105-6-294","article-title":"Harshlight: a \u201ccorrective make-up\u201d program for microarray chips.","volume":"6","author":"M Su\u00e1rez-Fari\u00f1as","year":"2005","journal-title":"BMC Bioinformatics."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"118-27","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods.","volume":"8","author":"W Johnson","year":"2007","journal-title":"Biostatistics."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"227-55","DOI":"10.1146\/annurev-immunol-032713-120225","article-title":"Immunology of psoriasis.","volume":"32","author":"M Lowes","year":"2014","journal-title":"Annu Rev Immunol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"4431-9","DOI":"10.4049\/jimmunol.176.7.4431","article-title":"The vast majority of CLA+ T cells are resident in normal skin.","volume":"176","author":"R Clark","year":"2006","journal-title":"J Immunol."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/4-149\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/4-149\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/4-149\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T07:36:20Z","timestamp":1543995380000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/4-149\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,11]]},"references-count":10,"URL":"https:\/\/doi.org\/10.12688\/f1000research.6581.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.7066.r9246","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.7066.r9578","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.7066.r9716","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.7066.r9426","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.7066.r9716","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.7066.r9246","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.7066.r9578","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.7066.r9426","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,11]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/4-149\/v1#article-reports","order":0,"name":"referee-status","label":"Referee 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and Immunology, School of Medicine, Duke University, Durham, NC, USA, 20 Jul 2015, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/4-149\/v1#referee-response-9578","order":2,"name":"referee-response-9578","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.7066.r9716, Luis Puig, Department of Dermatology, Hospital de Sant Pau, Barcelona, Spain, 30 Jul 2015, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/4-149\/v1#referee-response-9716","order":3,"name":"referee-response-9716","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This research was supported by National Institutes of Health (NIH) grant UL1 RR024143 from the National Center for Research Resources and the Milstein Medical Program.  NG was supported by a Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the NIH under award number T32GM07739 to the Weill Cornell\/Rockefeller\/Sloan-Kettering Tri-Institutional MD-PhD Program.  The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}