Journal Article

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

Lin, Nengxing, Wu, Yan, Chen, Wenmao, Zhang, Song, Wei, Wei, Chen, Xiaolu, Yu, Juanjuan, Zhang, Fangyuan, Zhang, Lingyun, Zhang, Jia

2021

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adoptive Transfer / Animals / Anti-Inflammatory Agents - pharmacology / Antibodies / Antimicrobial peptides / CD3 antigen / Cell activation / Connective tissue / Cytokines / Disease Models, Animal / Genes, T-Cell Receptor / HaCaT Cells / Humans / hyperforin / IL-17A / Imiquimod / Immunohistochemistry / Immunology / Infiltration / Inflammation / Interleukin 17 / Interleukin-17 - genetics / Interleukin-17 - metabolism / Intraepithelial Lymphocytes - drug effects / Intraepithelial Lymphocytes - immunology / Intraepithelial Lymphocytes - metabolism / Intraepithelial Lymphocytes - transplantation / Keratinocytes / Laboratory animals / Lymph nodes / Lymphatic system / Lymphocytes / Lymphocytes T / MAP kinase / Mental disorders / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Mice, Knockout / Mitogen-Activated Protein Kinases - metabolism / Pathogenesis / Phloroglucinol - analogs & derivatives / Phloroglucinol - pharmacology / Phosphorylation / Psoriasis / Psoriasis - chemically induced / Psoriasis - immunology / Psoriasis - metabolism / Psoriasis - prevention & control / Serum levels / Signal Transduction / Skin - drug effects / Skin - immunology / Skin - metabolism / Skin diseases / Skin lesions / Spleen / Splenocytes / Splenomegaly / Stat3 / Stat3 protein / STAT3 Transcription Factor - metabolism / Terpenes - pharmacology / Tumor necrosis factor-α / γδT cells