{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:43:25Z","timestamp":1790685805358,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K08484"],"award-info":[{"award-number":["21K08484"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K08672"],"award-info":[{"award-number":["20K08672"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K17442"],"award-info":[{"award-number":["20K17442"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Labour Sciences Research Grant","award":["20FC1047"],"award-info":[{"award-number":["20FC1047"]}]},{"DOI":"10.13039\/501100011907","name":"Mishima Kaiun Memorial Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100011907","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009158","name":"Kawasaki Medical School","doi-asserted-by":"publisher","award":["R03B-046"],"award-info":[{"award-number":["R03B-046"]}],"id":[{"id":"10.13039\/501100009158","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Eli Lilly (Japan)","award":["Eli Lilly Japan KK Research Grant 2021"],"award-info":[{"award-number":["Eli Lilly Japan KK Research Grant 2021"]}]},{"name":"UCB Japan","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and Apoe-deficient dyslipidemic mice, and administered a high-fat diet for 10 weeks to induce obesity. Imiquimod was applied to the ear for 5 days to induce psoriatic dermatitis. To examine the innate immune responses of NHEKs, we cultured and stimulated NHEKs using IL-17A, TNF-\u03b1, palmitic acid, and leptin. We found that obesity and dyslipidemia synergistically aggravated psoriatic dermatitis associated with increased gene expression of pro-inflammatory cytokines and chemokines. Treatment of NHEKs with palmitic acid and leptin amplified pro-inflammatory responses in combination with TNF-\u03b1 and IL-17A. Additionally, pretreatment with palmitic acid and leptin enhanced IL-17A-mediated c-Jun N-terminal kinase phosphorylation. These results revealed that obesity and dyslipidemia synergistically exacerbate psoriatic skin inflammation, and that metabolic-disorder-associated inflammatory factors, palmitic acid, and leptin augment the activation of epidermal keratinocytes. Our results emphasize that management of concomitant metabolic disorders is essential for preventing disease exacerbation in patients with psoriasis.<\/jats:p>","DOI":"10.3390\/ijms23084312","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T21:33:42Z","timestamp":1649885622000},"page":"4312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0154-5638","authenticated-orcid":false,"given":"Kenta","family":"Ikeda","sequence":"first","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan"},{"name":"Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki 701-0192, Japan"},{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-065X","authenticated-orcid":false,"given":"Shin","family":"Morizane","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Akagi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2653-9592","authenticated-orcid":false,"given":"Sumie","family":"Hiramatsu-Asano","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayano","family":"Yahagi","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Iseki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-1943","authenticated-orcid":false,"given":"Hideaki","family":"Kaneto","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-5188","authenticated-orcid":false,"given":"Katsuhiko","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0103-1621","authenticated-orcid":false,"given":"Tomoyuki","family":"Mukai","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki 701-0192, Japan"},{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s12016-018-8702-3","article-title":"The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis","volume":"55","author":"Blauvelt","year":"2018","journal-title":"Clin. 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