{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:33Z","timestamp":1787028513411,"version":"build-2736575974"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wisconsin Alumni Research Foundation","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]},{"name":"School of Pharmacy of the University of Wisconsin-Madison","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]},{"name":"Fall Research Competition at the University of Wisconsin\u2013Madison","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]},{"name":"UW SDRC","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]},{"name":"Summer Undergraduate Research Grant (URG) from Northwestern University","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]},{"name":"Laura and Edward Kremers Family Foundation","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]},{"name":"University of Wisconsin","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]},{"name":"Vilas Trust","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atopic dermatitis (AD) is a chronic inflammatory skin disease featuring skin barrier dysfunction and immune dysregulation. Previously, we reported that the retinoid-related orphan nuclear receptor ROR\u03b1 was highly expressed in the epidermis of normal skin. We also found that it positively regulated the expression of differentiation markers and skin barrier-related genes in human keratinocytes. In contrast, epidermal ROR\u03b1 expression was downregulated in the skin lesions of several inflammatory skin diseases, including AD. In this study, we generated mouse strains with epidermis-specific Rora ablation to understand the roles of epidermal ROR\u03b1 in regulating AD pathogenesis. Although Rora deficiency did not cause overt macroscopic skin abnormalities at the steady state, it greatly amplified MC903-elicited AD-like symptoms by intensifying skin scaliness, increasing epidermal hyperproliferation and barrier impairment, and elevating dermal immune infiltrates, proinflammatory cytokines, and chemokines. Despite the normal appearance at the steady state, Rora-deficient skin showed microscopic abnormalities, including mild epidermal hyperplasia, increased TEWL, and elevated mRNA expression of Krt16, Sprr2a, and Tslp genes, indicating subclinical impairment of epidermal barrier functions. Our results substantiate the importance of epidermal ROR\u03b1 in partially suppressing AD development by maintaining normal keratinocyte differentiation and skin barrier function.<\/jats:p>","DOI":"10.3390\/ijms241210241","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T08:56:01Z","timestamp":1686905761000},"page":"10241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Epidermal Loss of ROR\u03b1 Enhances Skin Inflammation in a MC903-Induced Mouse Model of Atopic Dermatitis"],"prefix":"10.3390","volume":"24","author":[{"given":"Xiangmei","family":"Hua","sequence":"first","affiliation":[{"name":"School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrad Dean","family":"Blosch","sequence":"additional","affiliation":[{"name":"Biomedical Research Model Services, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Dorsey","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria K.","family":"Ficaro","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L.","family":"Wallace","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Hsung","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA"},{"name":"UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-018-0001-z","article-title":"Atopic dermatitis","volume":"4","author":"Weidinger","year":"2018","journal-title":"Nat. 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