{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:52:57Z","timestamp":1773057177149,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Psoriasis is an immune-mediated inflammatory disease of the skin, which is characterized by epidermal hyperkeratosis and neutrophil infiltration. The interleukin (IL)-17\/IL-23 pathway and associated cytokines play major roles in the pathogenesis and exacerbation of psoriasis. The IL-18\/IL-18 receptor (R) \u03b1 signaling pathway is important for Th1 cytokine production and differentiation of Th1 cells; however, its role in the pathogenesis of psoriasis remains unknown. In this study, we investigated the effect of the IL-18R\u03b1-mediated signaling pathway in the pathogenesis of psoriasis in <jats:italic>Il18ra-<\/jats:italic>deficient mice (<jats:italic>Il18ra<\/jats:italic><jats:sup><jats:bold>\u2212<\/jats:bold>\/<jats:bold>\u2212<\/jats:bold><\/jats:sup>) and wild-type imiquimod (IMQ)-induced psoriatic dermatitis model mice. Blocking this pathway exacerbated IMQ-induced psoriatic skin inflammation. <jats:italic>Il18ra<\/jats:italic> deficiency led to significant increases in the levels of IL-1\u03b2, IL-6, IL-8, IL-17A, IL-23, and chemokine (C-X-C motif) ligand 2 in skin lesions. Gr1-positive cells highly infiltrated psoriatic skin lesions in <jats:italic>Il18ra<\/jats:italic><jats:sup><jats:bold>\u2212<\/jats:bold>\/<jats:bold>\u2212<\/jats:bold><\/jats:sup> mice compared to those in wild-type mice. Citrullinated histone H3-positive area was relatively broad in <jats:italic>Il18ra<\/jats:italic><jats:sup><jats:bold>\u2212<\/jats:bold>\/<jats:bold>\u2212<\/jats:bold><\/jats:sup> mice. These results suggest that IL-18R\u03b1-mediated signaling pathways may inhibit psoriatic skin inflammation by regulating infiltration and activation of neutrophil and other innate immune cells.<\/jats:p>","DOI":"10.3389\/fmed.2023.1293132","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T21:23:55Z","timestamp":1698528235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Blockade of IL-18R\u03b1-mediated signaling pathway exacerbates neutrophil infiltration in imiquimod-induced psoriasis murine model"],"prefix":"10.3389","volume":"10","author":[{"given":"Hiroki","family":"Akazawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Nozaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotaka","family":"Yamazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Ishimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chisato","family":"Ashida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akinori","family":"Okada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itaru","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/S0140-6736(14)61909-7","article-title":"Psoriasis","volume":"386","author":"Boehncke","year":"2015","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/1346-8138.14105","article-title":"Japanese Society for Psoriasis Research. 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