Overexpression of Hepatocyte Growth Factor in Dental Pulp Stem Cells Ameliorates the Severity of Psoriasis by Reducing Inflammatory Responses.

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.