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.