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Treatment for psoriasis mainly includes conventional immunosuppressive drugs. However, long-term treatment with global immunosuppressive agents may cause a variety of side effects, including nephrotoxicity and infections. Kaempferol, a natural flavonol present in various plants, is known to possess potent anti-inflammatory, anti-oxidant and anti-cancerous properties. However, it is unknown whether kaempferol is also anti-psoriatic. Here we established an imiquimod (IMQ)-induced psoriatic mouse model to explore the potential therapeutic effects of kaempferol on psoriatic skin lesions and inflammation. In this study, we demonstrated that treatment with kaempferol protected mice from developing psoriasis-like skin lesions induced by topical administration of IMQ. Kaempferol reduced CD3+ T cell infiltration and gene expression of major proinflammatory cytokines, including interleukin (IL)-6, IL-17A and tumor necrosis factor (TNF)-\u03b1, in the psoriatic skin lesion. It also down-regulated proinflammatory nuclear factor kappa B (NF-\u03baB) signaling in the skin. The therapeutic effects were associated with a significant increase in CD4+forkhead box protein 3 (FoxP3)+ regulatory T cell (Treg) frequency in the spleen and lymph nodes as well as FoxP3-positive staining in the skin lesion. Conversely, depletion of CD4+CD25+ Tregs reversed the therapeutic effects of kaempferol on the skin lesion. Kaempferol also lowered the percentage of IL-17A+CD4+ T cells in the spleen and lymph nodes of IMQ-induced psoriatic mice. Finally, kaempferol suppressed the proliferation of T cells in vitro and their mTOR signaling. Thus, our findings suggest that kaempferol may be a therapeutic drug for treating human psoriasis in the near future.<\/jats:p>","DOI":"10.1111\/cei.13363","type":"journal-article","created":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T07:13:52Z","timestamp":1565680432000},"page":"403-415","source":"Crossref","is-referenced-by-count":71,"title":["Kaempferol attenuates imiquimod-induced psoriatic skin inflammation in a mouse model"],"prefix":"10.1093","volume":"198","author":[{"given":"C","family":"Liu","sequence":"first","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Liu","sequence":"additional","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Lu","sequence":"additional","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Deng","sequence":"additional","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Yan","sequence":"additional","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Chen","sequence":"additional","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C-L","family":"Liang","sequence":"additional","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Wei","sequence":"additional","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Han","sequence":"additional","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6236-8105","authenticated-orcid":false,"given":"Z","family":"Dai","sequence":"additional","affiliation":[{"name":"Section of Immunology and Joint Immunology Program, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,26]]},"reference":[{"key":"2022011418370265800_cei13363-bib-0001","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1111\/bjd.13715","article-title":"The global burden of psoriatic skin disease","volume":"172","author":"Goff","year":"2015","journal-title":"Br J 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Correlation between their numbers and biologics-induced clinical improvement","volume":"21","author":"Richetta","year":"2011","journal-title":"Eur J Dermatol"},{"key":"2022011418370265800_cei13363-bib-0008","doi-asserted-by":"crossref","first-page":"164","DOI":"10.4049\/jimmunol.174.1.164","article-title":"Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation","volume":"174","author":"Sugiyama","year":"2005","journal-title":"J Immunol"},{"key":"2022011418370265800_cei13363-bib-0009","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1021\/jf000892m","article-title":"Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants","volume":"49","author":"Miean","year":"2001","journal-title":"J Agric Food 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