Dysfunction of regulatory T cells mediated by AKT-FOXO1 signaling pathway occurs during the development of psoriasis

Psoriasis is an immune-mediated skin disease with abnormal T cells. Regulatory T cells (Treg) are a kind of cell group with immunosuppressive effects. This study aimed to explore the role of Treg cells in the pathogenesis of psoriasis and its possible mechanism. Imiquimod induced psoriasis mice model was conducted. The skin lesions were evaluated according to the psoriasis area and severity index (PASI). Skin biopsies were taken for HE staining and immunohistochemical staining of IL-23, IL-17, IL-33 and TNF-α. CD4⁺CD25⁺ Treg cells were isolated. The proportions of Treg cells, cell proliferation, and immunosuppressive activity were analyzed by flow cytometry. The expression of AKT, Foxo1, pAKT, pFoxo1 protein, and the localization of Foxo1 protein in Treg cells were detected by western blot and immunofluorescence. The results showed that the psoriasis mice model was established successfully. There was no significant difference in the proportion of Treg cells between the two groups (P > 0.05). The cell proliferation abilities were decreased, and the immunosuppressive functions of Treg cells were weakened in the psoriatic group (P < 0.05). Western blot showed that pAKT and pFoxo1 levels of Treg cells were significantly increased in the psoriatic group (P < 0.05). Immunofluorescence showed that Foxo1 was mainly expressed in the nucleus of Treg cells in the control group, whereas expressed in the cytoplasm in the psoriasis group. Therefore, we concluded that the cell proliferation and immunosuppressive dysfunction of Treg cells mediated by AKT-FOXO1 signaling pathway may occurs during the development of psoriasis.