{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:49:30Z","timestamp":1783003770119,"version":"3.54.5"},"reference-count":101,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["PDIS00088"],"award-info":[{"award-number":["PDIS00088"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K16216"],"award-info":[{"award-number":["JP21K16216"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recent studies have highlighted the pathogenic roles of IL-17\u2013producing CD8+ T cells (T-cytotoxic 17 [Tc17]) in psoriasis. However, the underlying mechanisms of Tc17 induction remain unclear. In this study, we focused on the pathogenic subsets of Th17 and their mechanism of promotion of Tc17 responses. We determined that the pathogenic Th17-enriched fraction expressed melanoma cell adhesion molecule (MCAM) and CCR6, but not CD161, because this subset produced IL-17A abundantly and the presence of these cells in the peripheral blood of patients has been correlated with the severity of psoriasis. Intriguingly, the serial analysis of gene expression revealed that CCR6+MCAM+CD161\u2212CD4+ T cells displayed the gene profile for adaptive immune responses, including CD83, which is an activator for CD8+ T cells. Coculture assay with or without intercellular contact between CD4+ and CD8+ T cells showed that CCR6+MCAM+CD161\u2212CD4+ T cells induced the proliferation of CD8+ T cells in a CD83-dependent manner. However, the production of IL-17A by CD8+ T cells required exogenous IL-17A, suggesting that intercellular contact via CD83 and the production of IL-17A from activated CD4+ T cells elicit Tc17 responses. Intriguingly, the CD83 expression was enhanced in the presence of IL-15, and CD83+ cells stimulated with IL-1\u03b2, IL-23, IL-15, and IL-15R\u03b1 did not express FOXP3. Furthermore, CCR6+MCAM+CD161\u2212CD4+ T cells expressing CD83 were increased in the peripheral blood of patients, and the CD83+ Th17-type cells accumulated in the lesional skin of psoriasis. In conclusion, pathogenic MCAM+CD161\u2212 Th17 cells may be involved in the Tc17 responses via IL-17A and CD83 in psoriasis.<\/jats:p>","DOI":"10.4049\/jimmunol.2200530","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T14:52:52Z","timestamp":1682520772000},"page":"1867-1881","source":"Crossref","is-referenced-by-count":3,"title":["MCAM+CD161\u2212 Th17 Subset Expressing CD83 Enhances Tc17 Response in Psoriasis"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-6183","authenticated-orcid":false,"given":"Kohei","family":"Maeda","sequence":"first","affiliation":[{"name":"Division of Physiology and Pathology, Department of Pharmacology, Toxicology, and Therapeutics, Showa University School of Pharmacy , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8824-5162","authenticated-orcid":false,"given":"Toshihiro","family":"Tanioka","sequence":"additional","affiliation":[{"name":"Division of Physiology and Pathology, Department of Pharmacology, Toxicology, and Therapeutics, Showa University School of Pharmacy , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6494-4823","authenticated-orcid":false,"given":"Rei","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Physiology and Pathology, Department of Pharmacology, Toxicology, and Therapeutics, Showa University School of Pharmacy , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Showa University School of Medicine , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-7211","authenticated-orcid":false,"given":"Hirohiko","family":"Sueki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Showa University School of Medicine , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Takimoto","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Showa University School of Medicine , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University , Wakayama,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuho","family":"Ikeo","sequence":"additional","affiliation":[{"name":"DNA Data Analysis Laboratory, National Institute of Genetics , Shizuoka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-7974","authenticated-orcid":false,"given":"Yusuke","family":"Miwa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Showa University School of Medicine , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3871-6456","authenticated-orcid":false,"given":"Tsuyoshi","family":"Kasama","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Showa University School of Medicine , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanju","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Division of Physiology and Pathology, Department of Pharmacology, Toxicology, and Therapeutics, Showa University School of Pharmacy , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"2025021008072843200_r1","doi-asserted-by":"crossref","first-page":"E3422","DOI":"10.1073\/pnas.1400513111","article-title":"IL-17 drives psoriatic inflammation via distinct, target cell-specific mechanisms","volume":"111","author":"Ha","year":"2014","journal-title":"Proc. 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Immunol."},{"key":"2025021008072843200_r5","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1189\/JLB.0109046","article-title":"IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines","volume":"86","author":"Ortega","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"2025021008072843200_r6","doi-asserted-by":"crossref","first-page":"e20191397","DOI":"10.1084\/jem.20191397","article-title":"Interleukin-17 cytokines: effectors and targets in psoriasis\u2014a breakthrough in understanding and treatment","volume":"217","author":"Prinz","year":"2020","journal-title":"J. Exp. 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