{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:29:23Z","timestamp":1792250963962,"version":"4.4.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"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. Immunol."],"abstract":"<jats:p>\n                    Hyperforin is a major active constituent of\n                    <jats:italic>Hypericum perforatum<\/jats:italic>\n                    \u00a0L. extract, which is widely used for the treatment of depressive disorders. Recent studies have reported that hyperforin reduced inflammation in stroke and suppressed proliferation and differentiation in keratinocytes. Psoriasis is a chronic immune-mediated inflammatory skin disease in which the IL-23\/IL-17 axis plays an important role. To investigate the underlying inflammatory mechanisms and response of hyperforin in psoriasis, we use imiquimod (IMQ)-induced mice model,\n                    <jats:italic>in vitro<\/jats:italic>\n                    cultured murine splenic \u03b3\u03b4 T cells, and HaCaT cells in this study. Data showed that hyperforin reduced epidermal thickness and decreased IMQ-induced pathological scores of cutaneous skin lesions in mice. Meanwhile we proved that hyperforin suppressed infiltration of CD3\n                    <jats:sup>+<\/jats:sup>\n                    T cells and downregulated expression of\n                    <jats:italic>Il1<\/jats:italic>\n                    ,\n                    <jats:italic>Il6<\/jats:italic>\n                    ,\n                    <jats:italic>Il23<\/jats:italic>\n                    ,\n                    <jats:italic>Il17a<\/jats:italic>\n                    ,\n                    <jats:italic>Il22<\/jats:italic>\n                    , antimicrobial peptides (AMPs) in the skin lesion. Hyperforin significantly inhibited imiquimod-induced splenomegaly, reduced serum levels of TNF-\u03b1 and IL-6, and IL-17A in splenocytes and draining lymph nodes. Our study also suggested that hyperforin lessened the infiltration of \u03b3\u03b4 T cell and CCR6\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells in spleen and lymph nodes. Hyperforin also suppressed the typical psoriasis-like inflammatory responses and the infiltration of IL-17A\n                    <jats:sup>+<\/jats:sup>\n                    cells in dermal \u03b3\u03b4 T cells of IMQ treated\n                    <jats:italic>Tcrd<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice transferred with \u03b3\u03b4 T cells.\n                    <jats:italic>In vitro<\/jats:italic>\n                    studies, hyperforin reduced the expression and secretion of IL-17A in \u03b3\u03b4 T cells, and suppressed the activation of MAPK\/STAT3 pathways in human keratinocyte HaCaT cells and \u03b3\u03b4 T cells. In conclusion, hyperforin alleviates IMQ-induced inflammation in psoriasis through suppressing the immune responses exerted by IL-17 A-producing \u03b3\u03b4 T cells and related cytokines by modulating MAPK\/STAT3 pathways. Our study provided a novel therapeutic tragedy for psoriasis by which hyperforin attenuates psoriasis-related inflammatory responses.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.635076","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:36:56Z","timestamp":1620175016000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A\u2013Producing \u03b3\u03b4 T Cells"],"prefix":"10.3389","volume":"12","author":[{"given":"Song","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nengxing","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61909-7","article-title":"Psoriasis","volume":"386","author":"Boehncke","year":"2015","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e20191317","DOI":"10.1084\/jem.20191397","article-title":"Interleukin-17 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