{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:23:35Z","timestamp":1791501815846,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a Grant-in-Aid for Scientific Research","award":["no. 20K08672"],"award-info":[{"award-number":["no. 20K08672"]}]},{"name":"a Grant-in-Aid for Research Activity Start-up","award":["No.20K22739"],"award-info":[{"award-number":["No.20K22739"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interleukin (IL) 23 (p19\/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. In clinical practice, anti-IL-23Ap19 antibodies are highly effective against psoriasis. IL-39 (p19\/ Epstein-Barr virus-induced (EBI) 3), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. Anti-IL-23Ap19 antibodies may bind to IL-39; also, the cytokine may contribute to the pathogenesis of psoriasis. To investigate IL23Ap19- and\/or EBI3-including cytokines in psoriatic keratinocytes, we analyzed IL-23Ap19 and EBI3 expressions in psoriasis skin lesions, using immunohistochemistry and normal human epidermal keratinocytes (NHEKs) stimulated with inflammatory cytokines, using quantitative real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-electrospray tandem mass spectrometry (LC-Ms\/Ms). Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-\u03b1, IL-17A, and interferon (IFN)-\u03b3, and suppressed by dexamethasone, vitamin D3, and acitretin. In ELISA and LC-Ms\/Ms analyses, keratinocyte-derived IL-23Ap19 and EBI3, but not heterodimeric forms, were detected with humanized anti-IL-23Ap19 monoclonal antibodies, tildrakizumab, and anti-EBI3 antibodies, respectively. Psoriatic keratinocytes may express IL-23Ap19 and EBI3 proteins in a monomer or homopolymer, such as homodimer or homotrimer.<\/jats:p>","DOI":"10.3390\/ijms222312659","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T04:48:37Z","timestamp":1638247717000},"page":"12659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multifaceted Analysis of IL-23A- and\/or EBI3-Including Cytokines Produced by Psoriatic Keratinocytes"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3896-5732","authenticated-orcid":false,"given":"Kota","family":"Tachibana","sequence":"first","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"},{"name":"Department of Dermatology, Southern Medical University Zhujiang Hospital, 253 Gongye Middle Ave, Guangzhou 510280, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Urakami","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Kajita","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Kobashi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minori","family":"Sasakura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Sugihara","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahoko","family":"Tomonobu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0566-4872","authenticated-orcid":false,"given":"Masakiyo","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Ouchida","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, 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 Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jaci.2017.07.004","article-title":"Psoriasis pathogenesis and the development of novel targeted immune therapies","volume":"140","author":"Hawkes","year":"2017","journal-title":"J. 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