{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:08:16Z","timestamp":1789103296620,"version":"build-2803163510"},"reference-count":19,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shionogi & Co., Ltd."},{"id":[{"id":"https:\/\/ror.org\/01v3bqg10","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Atopic dermatitis (AD) is characterized by pruritus and epidermal barrier dysfunction. Tapinarof, a therapeutic aryl hydrocarbon receptor (AHR)-modulating agent, is clinically effective in AD, but its mechanisms in allergen-driven models remain unclear. We evaluated tapinarof in a Dermatophagoides farinae (Df)-induced murine model of AD, focusing on AHR-mediated barrier restoration. AD-like dermatitis was induced in female NC\/Nga mice, followed by daily topical tapinarof or betamethasone for four days. Disease severity, transepidermal water loss (TEWL), histopathology, and gene\/protein expression were assessed. Tapinarof significantly reduced dermatitis scores and TEWL and, unlike betamethasone, preserved epidermal architecture without suppressing ear swelling. Tapinarof upregulated the AHR-responsive genes Cyp1a1 and Nqo1 and induced Ovol1, an epidermal differentiation-associated transcription factor, with increased CYP1A1, NRF2, NQO1, and OVOL1 protein expression. Tapinarof markedly increased filaggrin (FLG)- and loricrin (LOR)-positive areas in lesional skin compared with vehicle (FLG: 11.3% vs. 3.1%; LOR: 18.9% vs. 3.9%; both p &lt; 0.05), restoring FLG to a level comparable to the no-treatment control, while LOR significantly exceeded it. These findings indicate that tapinarof may restore skin barrier function in allergen-induced AD via AHR-NRF2 and AHR-OVOL1 signaling, supporting its potential as a steroid-sparing topical therapy for long-term AD management.<\/jats:p>","DOI":"10.3390\/ijms27188032","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:02:48Z","timestamp":1788962568000},"page":"8032","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Therapeutic Aryl Hydrocarbon Receptor-Modulating Agent Tapinarof Restores Skin Barrier Dysfunction in a Mite Antigen-Induced Murine Model of Atopic Dermatitis"],"prefix":"10.3390","volume":"27","author":[{"given":"Gaku","family":"Tsuji","sequence":"first","affiliation":[{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"},{"name":"Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-8449","authenticated-orcid":false,"given":"Masaki","family":"Takemura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Koji","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2198-8965","authenticated-orcid":false,"given":"Ayako","family":"Yumine","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5881-4726","authenticated-orcid":false,"given":"Noriko","family":"Konishi","sequence":"additional","affiliation":[{"name":"Biological\/Pharmacological Research Laboratories, Shionogi Takatsuki Research Center, Shionogi & Co., Ltd., Osaka 569-1125, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2811-8273","authenticated-orcid":false,"given":"Takeshi","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0140-6736(20)31286-1","article-title":"Atopic dermatitis","volume":"396","author":"Langan","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"416","DOI":"10.4103\/2229-5178.142483","article-title":"Side-effects of topical steroids: A long overdue revisit","volume":"5","author":"Coondoo","year":"2014","journal-title":"Indian Dermatol. 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