{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:47:18Z","timestamp":1792446438127,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007605","name":"Aarhus Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chronic inflammatory skin diseases such as psoriasis and hidradenitis suppurativa are driven by cytokines, including IL\u201017A and TNF. Although biologics targeting these cytokines have transformed therapy, the transcriptional contributions of individual skin\u2010resident cell types remain unclear, and dermal fibroblasts have been largely overlooked compared with keratinocytes. To address this, we compared the transcriptional responses of primary human dermal fibroblasts and keratinocytes following in\u00a0vitro stimulation with IL\u201017A, TNF, or both, using bulk RNA sequencing and Western blotting. Dermal fibroblasts mounted a stronger and broader proinflammatory response than keratinocytes. This was particularly evident in response to TNF and combined TNF\/IL\u201017A stimulation, with enrichment for immune signalling and chemotaxis pathways and robust induction of chemokine genes, including\n                    <jats:italic>CCL20<\/jats:italic>\n                    ,\n                    <jats:italic>CXCL8<\/jats:italic>\n                    , and\n                    <jats:italic>IL6<\/jats:italic>\n                    . Keratinocytes primarily upregulated genes associated with epithelial differentiation, barrier function, and protein regulation, including\n                    <jats:italic>IL36G<\/jats:italic>\n                    ,\n                    <jats:italic>S100A7A<\/jats:italic>\n                    , and\n                    <jats:italic>DEFB4A<\/jats:italic>\n                    . The heightened fibroblast responsiveness correlated with increased TNF sensitivity and substantially higher TNFR2 (\n                    <jats:italic>TNFRSF1B<\/jats:italic>\n                    ) expression and signalling compared with keratinocytes, suggesting a fibroblast\u2010specific mechanism amplifying inflammatory responses. These findings challenge the keratinocyte\u2010centric view of skin inflammation and identify dermal fibroblasts as active contributors and potential therapeutic targets in TNF\u2010 and Th17\u2010driven skin diseases.\n                  <\/jats:p>","DOI":"10.1111\/exd.70232","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:32:16Z","timestamp":1772965936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dermal Fibroblasts, Not Keratinocytes, Dominate IL\u201017A\/TNF\u2010Driven Inflammation"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2946-9163","authenticated-orcid":false,"given":"Lejla","family":"Svraka","sequence":"first","affiliation":[{"name":"Department of Dermatology Aarhus University Hospital  Aarhus Denmark"},{"name":"Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4610-5428","authenticated-orcid":false,"given":"Hakim Ben","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Department of Dermatology Aarhus University Hospital  Aarhus Denmark"},{"name":"Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-1991","authenticated-orcid":false,"given":"Trine","family":"Bertelsen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Aarhus University Hospital  Aarhus Denmark"},{"name":"Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-3158","authenticated-orcid":false,"given":"Christian","family":"Vestergaard","sequence":"additional","affiliation":[{"name":"Department of Dermatology Aarhus University Hospital  Aarhus Denmark"},{"name":"Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5665-5212","authenticated-orcid":false,"given":"Claus","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Aarhus University Hospital  Aarhus Denmark"},{"name":"Aarhus University  Aarhus 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