Psoriasis is an autoimmune disease still lacking standard treatment, and it has been demonstrated that mesenchymal stem cells (MSCs) are capable of immunoregulation. The underlying mechanism might involve the secretion of soluble cytokines, such as hepatocyte growth factor (HGF). This study aims to investigate the therapeutic effect of HGF-overexpressed dental pulp stem cells (DPSCs) [DPSCs; HGF overexpressed DPSCs (HGF-DPSCs)] on imiquimod-induced psoriasis. DPSCs were isolated and transfected by adenovirus vector carrying HGF gene (Ad-HGF). The immunoregulatry abilities of DPSCs and HGF-DPSCs were investigated by coculture of the MSCs with peripheral blood mononuclear cells (PBMCs) under appropriated stimulation. The psoriatic mice were treated with saline control, DPSCs, or HGF-DPSCs. Then the mice spleens were collected and weighted. The psoriatic skin lesions were analyzed by Hematoxylin/Eosin and immunohistochemical staining for histopathological changes, and quantitative real-time polymerase chain reaction to detect the expression levels of CD4⁺ T cell-related transcription factors and cytokines. The mice blood serum was measured by MILLIPLEX analysis and enzyme-linked immunosorbent assay to evaluate the expression levels of inflammation cytokines. The coculture experiments showed HGF overexpression enhanced the immunoregulation abilities of DPSCs not by suppressing PBMCs' proliferation, but by downregulating T helper 1 (Th1), Th17 cells, and upregulating regulatory T (Treg) cells. In psoriatic skin lesions, the psoriasis-like erythema, scaling, and thickening were ameliorated; and the expression of cytokeratin 6 (CK6), and cytokeratin 17 (CK17) were downregulated by DPSCs and HGF-DPSCs treatment. HGF overexpression enhanced the decrease of spleen masses; enhanced the downregulation of the expression levels of interferon-gamma (IFN-γ), tumor necrosis factor-α, and interleukin (IL)-17A in the blood serums; enhanced the downregulation of T-box transcription factor 21 (T-bet), IFN-γ, retinoic acid-related orphan receptor-γt (RORγt), IL-17A, IL-17F, IL-23, and upregulation of Foxp3 and IL-10 in the psoriatic skin lesions. Therefore, HGF overexpression enhanced DPSCs' treatment effect on psoriasis mainly by reducing inflammatory responses. These findings might provide new immunoregulation strategies for psoriasis treatment.

中文翻译：

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牙髓干细胞中肝细胞生长因子的过表达通过减少炎症反应来改善银屑病的严重程度

银屑病是一种自身免疫性疾病，目前仍缺乏标准治疗，间充质干细胞 (MSCs) 已被证明具有免疫调节能力。潜在机制可能涉及可溶性细胞因子的分泌，例如肝细胞生长因子 (HGF)。本研究旨在探讨HGF过表达的牙髓干细胞 (DPSCs) [DPSCs; HGF过表达的 DPSCs (HGF-DPSCs)] 对咪喹莫特诱导的银屑病。分离DPSCs并用携带HGF的腺病毒载体转染基因（Ad-HGF）。通过在适当的刺激下将 MSCs 与外周血单核细胞 (PBMCs) 共培养，研究了 DPSCs 和 HGF-DPSCs 的免疫调节能力。银屑病小鼠用盐水对照、DPSC 或 HGF-DPSC 治疗。然后收集小鼠脾脏并称重。银屑病皮损采用苏木精/伊红和免疫组织化学染色分析组织病理学变化，实时定量聚合酶链反应检测CD4+T细胞相关^转录因子和细胞因子的表达水平。通过MILLIPLEX分析和酶联免疫吸附测定法测量小鼠血清以评估炎症细胞因子的表达水平。共培养实验显示HGF过表达增强 DPSC 的免疫调节能力不是通过抑制 PBMC 的增殖，而是通过下调 T 辅助细胞 1 (Th1)、Th17 细胞和上调调节性 T (Treg) 细胞。在银屑病皮损中，银屑病样红斑、脱屑和增厚得到改善；细胞角蛋白 6 (CK6) 和细胞角蛋白 17 (CK17) 的表达被 DPSC 和 HGF-DPSC 处理下调。HGF过表达促进了脾肿块的减少；增强血清中干扰素-γ (IFN-γ)、肿瘤坏死因子-α 和白细胞介素 (IL)-17A 表达水平的下调；增强T-box转录因子 21 ( T-bet )、IFN-γ的下调、视黄酸相关孤儿受体-γt ( RORγt )、IL-17A、IL-17F、IL-23，以及银屑病皮损中Foxp3和IL-10的上调。因此，HGF过表达主要通过降低炎症反应来增强DPSCs对银屑病的治疗作用。这些发现可能为银屑病治疗提供新的免疫调节策略。