{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:06:12Z","timestamp":1791237972647,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Psoriasis vulgaris<\/jats:italic> is an inflammatory skin disease that affects 2%\u20133% of the population worldwide. One of the major challenges in discovering novel therapies is the poor translatability of animal models to human disease. Therefore, it is imperative to develop human preclinical models of psoriasis that are amenable to pharmacological intervention. Here, we report a 3\u2010D reconstituted human epidermis (RHE) culture system treated with cytokines commonly associated with psoriasis (TNF\u03b1, IL\u201017A and IL\u201022) that reproduced some key features of the human disease. The effects on epidermal morphology, gene transcription and cytokine production, which are dysregulated in psoriasis were assessed. Certain morphological features of psoriatic epidermis were evident in cytokine\u2010stimulated RHEs, including hypogranulosis and parakeratosis. In addition, RHEs responded to a cytokine mix in a dose\u2010dependent manner by expressing genes and proteins associated with impaired keratinocyte differentiation (keratin 10\/K10, loricrin), innate immune responses (<jats:italic>S100A7<\/jats:italic>, <jats:italic>DEFB4<\/jats:italic>, <jats:italic>elafin<\/jats:italic>) and inflammation (<jats:italic>IL\u20101\u03b1<\/jats:italic>, <jats:italic>IL\u20106<\/jats:italic>, <jats:italic>IL\u20108<\/jats:italic>, <jats:italic>IL\u201010<\/jats:italic>, <jats:italic>IL\u201012<\/jats:italic>\/<jats:italic>23p40<\/jats:italic>, <jats:italic>IL\u201036\u03b3<\/jats:italic>, <jats:italic>GM\u2010CSF<\/jats:italic> and <jats:italic>IFN\u03b3<\/jats:italic>) typical of psoriasis. These disease\u2010relevant changes in morphology, gene transcription and cytokine production were robustly attenuated by pharmacologically blocking TNF\u03b1\/IL\u201017A\u2010induced NF\u2010\u03baB activation with IKK\u20102 inhibitor IV. Conversely, inhibition of IL\u201022\u2010induced JAK1 signalling with ABT\u2010317 strongly attenuated morphological features of the disease but had no effect on NF\u03baB\u2010dependent cytokine production, suggesting distinct mechanisms of action by the cytokines driving psoriasis. These data support the use of cytokine\u2010induced RHE models for identifying and targeting keratinocyte signalling pathways important for disease progression and may provide translational insights into novel keratinocyte mechanisms for novel psoriasis therapies.<\/jats:p>","DOI":"10.1111\/exd.14551","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T21:17:08Z","timestamp":1645823828000},"page":"1036-1047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cytokine induced 3\u2010D organotypic psoriasis skin model demonstrates distinct roles for NF\u2010\u03baB and JAK pathways in disease pathophysiology"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1428-6973","authenticated-orcid":false,"given":"Viktor","family":"Todorovi\u0107","sequence":"first","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heath A.","family":"McDonald","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Hoover","sequence":"additional","affiliation":[{"name":"Department of Dermatology Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph B.","family":"Wetter","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia E.","family":"Marinopoulos","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa L.","family":"Woody","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loan","family":"Miller","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Finkielsztein","sequence":"additional","affiliation":[{"name":"Department of Dermatology Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4652-434X","authenticated-orcid":false,"given":"Robert W.","family":"Dunstan","sequence":"additional","affiliation":[{"name":"AbbVie Bioresearch Center  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Paller","sequence":"additional","affiliation":[{"name":"Department of Dermatology Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prisca","family":"Honore","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spiro","family":"Getsios","sequence":"additional","affiliation":[{"name":"Department of Dermatology Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E.","family":"Scott","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041320"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14433"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041257"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120225"},{"issue":"5","key":"e_1_2_9_6_1","first-page":"6","article-title":"Update on the pathophysiology of psoriasis","volume":"102","author":"Hugh 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