The distinct role and regulatory mechanism of IL-17 and IFN-γ in the initiation and development of plaque vs guttate psoriasis.

ABSTRACT

BACKGROUND: Few studies have explored the differences of immunopathogenesis in plaque vs guttate psoriasis, especially on the inhibitory role of regulatory T cells (Tregs) on IL-17/ IFN-γ production and the impact of CD4+T cells on keratinocytes. OBJECTIVE: To investigate the percentage and inhibitory function of CD4+CD25highTreg and differential expressions of IL-17/ IFN-γ in plaque vs guttate psoriasis, and the effects of CD4+T cells on the proliferation of keratinocytes. METHODS: Peripheral blood mononuclear cells (PBMCs) were prepared from patients with the plaque and guttate psoriasis. The percentage of CD4+CD25high Tregs, IL-17/IFN-γ- producing CD4+ or CD8+T cells, and apoptosis and cell cycle of Hacat cells were determined by flow cytometry. The level of IFN-γ in supernatants was analyzed by ELISA. RESULTS: The percentage of CD4+CD25highTregs in plaque psoriasis was significantly increased, and they can inhibit IFN-γ production from CD4+CD25- effector T cells. The percentage of CD8+IFN-γ+cells was also significantly increased in plaque psoriasis, and these cells positively correlated with disease severity. The percentage of CD4+CD25highTregs was decreased and CD4+IFN-γ+/IFN-γ+IL-17+ cells were predominantly increased in guttate psoriasis. CD4+T cells from guttate psoriasis induce apoptosis of keratinocytes while they promote the proliferation of keratinocytes in plaque psoriasis by decreasing late apoptosis and increasing the percentage of G1 phase. CONCLUSION: There was considerable discrepancy of the phenotype and function of T cells between plaque vs guttate psoriasis. IFN-γ and IL-17 from CD4+T cells play a crucial role in guttate psoriasis, however, IFN-γ and IL-17 from CD8+T cells are more important in the immunopathogenesis of plaque psoriasis.