A four-herb topical formula attenuates psoriasis-like skin inflammation by suppressing IL-17-mediated inflammation and pathogenic γδT17 cell infiltration

Background Psoriasis is a chronic immune-mediated inflammatory skin disease driven by dysregulation of IL-17-mediated immune responses. Current topical therapies, including corticosteroids, are limited by long-term side effects, creating demand for safer alternatives. DH-YH is a novel four-herb Traditional Chinese Medicine (TCM) formula derived from Duhuo Jisheng Tang, comprising Angelica pubescens , Gentiana macrophylla , Taxillus chinensis , and Paeonia lactiflora . Based on an initial clinical observation of improvement following topical DH-YH treatment in a patient with psoriasis, this study investigated its immunomodulatory effects in psoriasis-related models. Methods The anti-inflammatory effects of DH-YH were assessed in vitro using IL-17A-stimulated human keratinocytes (HaCaT cells) and LPS-activated bone marrow-derived dendritic cells (BMDCs) and RAW264.7 macrophages. The effects on T-cell polarization were evaluated in murine splenic CD4 + T cells differentiated toward Th1, Th2, and Th17 lineages. In vivo , an imiquimod (IMQ)-induced psoriasis-like mouse model (BALB/c, n = 5/group) was used to evaluate topical DH-YH ointment. Skin histopathology (H&E staining) and multi-organ flow cytometric analysis (skin, spleen, and lymph nodes) were performed to assess epidermal thickness, inflammatory infiltration, and immune cell subset frequencies. Results Topical DH-YH ointment markedly improved psoriatic lesions in a clinical case without hepatorenal toxicity. In vitro , DH-YH dose-dependently suppressed IL-8 secretion in IL-17A-stimulated HaCaT cells and inhibited TNF-α and IL-6 production in LPS-activated BMDCs. DH-YH also significantly reduced Th17 and Th2 cell differentiation without affecting cell viability. In the IMQ-induced mouse model, topical DH-YH significantly reduced epidermal thickness and dermal inflammatory cell infiltration. Flow cytometric analysis revealed that DH-YH specifically decreased the proportions of CD45 + , CD3 + , γδT, and γδT17 cells in lesional skin. Conclusion DH-YH attenuates psoriasis-related inflammatory responses across multiple cellular and immune components, including keratinocyte inflammatory responses, BMDC cytokine production, T helper cell differentiation, and γδT17 cell accumulation.