{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:30:03Z","timestamp":1791495003496,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Psoriasis is a chronic skin disease affecting 2\u20133% of the global population. The proinflammatory IL-17A is a key cytokine in psoriasis. Accumulating evidence has revealed that IL-36\u03b3 plays also a pathogenic role. To understand more precisely the role of the IL-17A\u2013IL-36\u03b3 cytokine network in skin pathology, we used an ear injection model. We injected IL-17A or IL-36\u03b3 alone and in combination into the ear pinnae of mice. This resulted in a significant increase in ear thickness measured over time. Histological evaluation of IL-17A + IL-36\u03b3-treated skin showed a strong acanthosis, hyperparakeratosis and infiltration of neutrophils. The same histological features were found in mice after injection of IL-36\u03b3 alone, but to a lesser extent. IL-17A alone was not able to induce psoriasis-like changes. Genes encoding proteins of the S100 family, antimicrobial peptides and chemo-attractants for neutrophils were upregulated in the IL-17A + IL-36\u03b3 group. A much weaker expression was seen after the injection of each cytokine alone. These results strengthen the hypothesis that IL-17A and IL-36\u03b3 drive psoriatic inflammation via a synergistic interaction. Our established intradermal ear injection model can be utilized in the future to monitor effects of various inhibitors of this cytokine network.<\/jats:p>","DOI":"10.3390\/life11080846","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:11:49Z","timestamp":1629331909000},"page":"846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Establishment of an Intradermal Ear Injection Model of IL-17A and IL-36\u03b3 as a Tool to Investigate the Psoriatic Cytokine Network"],"prefix":"10.3390","volume":"11","author":[{"given":"David","family":"Kluwig","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Department of Dermatology and Allergology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Huth","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8768-3232","authenticated-orcid":false,"given":"Ali T.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center for Clinical Research (IZKF), Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina M.","family":"Pfaff","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Department of Dermatology and Allergology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Fietkau","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Huth","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Marquardt","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens M.","family":"Baron","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"L\u00fcscher","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/S0140-6736(21)00184-7","article-title":"Therapeutics Targeting the IL-23 and IL-17 Pathway in Psoriasis","volume":"397","author":"Ghoreschi","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1046\/j.1523-1747.1999.00749.x","article-title":"The Majority of Epidermal T Cells in Psoriasis Vulgaris Lesions Can Produce Type 1 Cytokines, Interferon-\u03b3, Interleukin-2, and Tumor Necrosis Factor-\u03b1, Defining TC1 (Cytotoxic T Lymphocyte) and TH1 Effector Populations: A Type 1 Differentiation Bias Is also measured in curculating blood T cells in psoriatic patients","volume":"113","author":"Austin","year":"1999","journal-title":"J. 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