{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:33:45Z","timestamp":1786962825092,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"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. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Psoriasis is a T help 17 (Th17) cell-mediated chronic inflammatory skin disease. Recent studies have shown that dihydroartemisinin (DHA) can significantly reduce experimental autoimmune encephalomyelitis and rheumatoid arthritis by regulating Th17 cells.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> To verify whether DHA can improve the symptoms of psoriasis and to further explore the possible mechanism.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The efficiency of DHA was preliminary detected on human keratinocytes (HaCaT) cells in psoriatic condition. Then, imiquimod-induced psoriasis-like model in BALB\/c mice was established to evaluate the effects of DHA <jats:italic>in vivo<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Under the stimulation of tumor necrosis factor-\u03b1 (TNF-\u03b1) and interferon-\u03b3 (IFN-\u03b3), DHA inhibited the proliferation of HaCaT cells and significantly affected the mRNA expression levels of IFN-\u03b3, interleukin (IL), IL-17A and IL-23. DHA treatment reduced the severity of psoriasis-like skin and resulted in less infiltration of immune cells in skin lesions. DHA restored the expression of IFN-\u03b3, IL-17A, and IL-23 in skins, as well as a decrease of cytokines and chemokines in skin supernatant. DHA also altered the cellular composition in the spleen, which is the makeup of the T cells, dendritic cells (DCs), and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and the expression of Th17 cell-related transcription factors retinoid-related orphan receptor-gamma t (ROR-\u03b3t) <jats:italic>in vitro<\/jats:italic>. In addition, phosphorylation of signal transducer and activator of transcription-3 (STAT3) was significantly reduced in DHA treatment mice, suggesting that the IL-23\/Th17 axis plays a pivotal role.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> DHA inhibits the progression of psoriasis by regulating IL-23\/Th17 axis and is expected to be an effective drug for the treatment of psoriasis.<\/jats:p>","DOI":"10.3389\/fphar.2021.704481","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T05:01:41Z","timestamp":1629090101000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Dihydroartemisinin Alleviates Imiquimod-Induced Psoriasis-like Skin Lesion in Mice Involving Modulation of IL-23\/Th17 Axis"],"prefix":"10.3389","volume":"12","author":[{"given":"Jiang-Min","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan-Xin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Fang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Bo","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Hai","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian-Hua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan-Ping","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Gao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Hua","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1136\/annrheumdis-2013-204782","article-title":"IL-17A Gene Transfer Induces Bone Loss and Epidermal Hyperplasia Associated with Psoriatic Arthritis","volume":"74","author":"Adamopoulos","year":"2015","journal-title":"Ann. 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