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Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A–Producing γδ T Cells

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Title: Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A–Producing γδ T Cells
Authors: Song Zhang, Jia Zhang, Juanjuan Yu, Xiaolu Chen, Fangyuan Zhang, Wei Wei, Lingyun Zhang, Wenmao Chen, Nengxing Lin, Yan Wu
Source: Frontiers in Immunology, Vol 12 (2021)
Publisher Information: Frontiers Media S.A., 2021.
Publication Year: 2021
Collection: LCC:Immunologic diseases. Allergy
Subject Terms: IL-17A, psoriasis, hyperforin, γδT cells, Stat3, Immunologic diseases. Allergy, RC581-607
More Details: Hyperforin is a major active constituent of Hypericum perforatum L. 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, in vitro cultured murine splenic γδ 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+ T cells and downregulated expression of Il1, Il6, Il23, Il17a, Il22, antimicrobial peptides (AMPs) in the skin lesion. Hyperforin significantly inhibited imiquimod-induced splenomegaly, reduced serum levels of TNF-α and IL-6, and IL-17A in splenocytes and draining lymph nodes. Our study also suggested that hyperforin lessened the infiltration of γδ T cell and CCR6+ γδ T cells in spleen and lymph nodes. Hyperforin also suppressed the typical psoriasis-like inflammatory responses and the infiltration of IL-17A+ cells in dermal γδ T cells of IMQ treated Tcrd−/− mice transferred with γδ T cells. In vitro studies, hyperforin reduced the expression and secretion of IL-17A in γδ T cells, and suppressed the activation of MAPK/STAT3 pathways in human keratinocyte HaCaT cells and γδ T cells. In conclusion, hyperforin alleviates IMQ-induced inflammation in psoriasis through suppressing the immune responses exerted by IL-17 A-producing γδ 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-3224
Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2021.635076/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2021.635076
Access URL: https://doaj.org/article/6d1a0d983c2f4913819e9e734b9a162c
Accession Number: edsdoj.6d1a0d983c2f4913819e9e734b9a162c
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  Data: Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A–Producing γδ T Cells
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  Data: <searchLink fieldCode="AR" term="%22Song+Zhang%22">Song Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Jia+Zhang%22">Jia Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Juanjuan+Yu%22">Juanjuan Yu</searchLink><br /><searchLink fieldCode="AR" term="%22Xiaolu+Chen%22">Xiaolu Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Fangyuan+Zhang%22">Fangyuan Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Wei+Wei%22">Wei Wei</searchLink><br /><searchLink fieldCode="AR" term="%22Lingyun+Zhang%22">Lingyun Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Wenmao+Chen%22">Wenmao Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Nengxing+Lin%22">Nengxing Lin</searchLink><br /><searchLink fieldCode="AR" term="%22Yan+Wu%22">Yan Wu</searchLink>
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  Data: Frontiers in Immunology, Vol 12 (2021)
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  Data: LCC:Immunologic diseases. Allergy
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  Data: Hyperforin is a major active constituent of Hypericum perforatum L. 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, in vitro cultured murine splenic γδ 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+ T cells and downregulated expression of Il1, Il6, Il23, Il17a, Il22, antimicrobial peptides (AMPs) in the skin lesion. Hyperforin significantly inhibited imiquimod-induced splenomegaly, reduced serum levels of TNF-α and IL-6, and IL-17A in splenocytes and draining lymph nodes. Our study also suggested that hyperforin lessened the infiltration of γδ T cell and CCR6+ γδ T cells in spleen and lymph nodes. Hyperforin also suppressed the typical psoriasis-like inflammatory responses and the infiltration of IL-17A+ cells in dermal γδ T cells of IMQ treated Tcrd−/− mice transferred with γδ T cells. In vitro studies, hyperforin reduced the expression and secretion of IL-17A in γδ T cells, and suppressed the activation of MAPK/STAT3 pathways in human keratinocyte HaCaT cells and γδ T cells. In conclusion, hyperforin alleviates IMQ-induced inflammation in psoriasis through suppressing the immune responses exerted by IL-17 A-producing γδ 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.
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        Value: 10.3389/fimmu.2021.635076
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      – Text: English
    Subjects:
      – SubjectFull: IL-17A
        Type: general
      – SubjectFull: psoriasis
        Type: general
      – SubjectFull: hyperforin
        Type: general
      – SubjectFull: γδT cells
        Type: general
      – SubjectFull: Stat3
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      – TitleFull: Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A–Producing γδ T Cells
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