Psoriasis

Abstract

Psoriasis vulgaris is a chronic, debilitating skin disease that affects millions of people worldwide. Although many components, including keratinocytes, dendritic cells (DCs), T cells, neutrophils, and endothelial cells are involved in psoriasis lesional skins, it is an inflammatory skin disease mainly mediated by T cells and DCs. Psoriatic skin contains diversified T cell and dendritic cell populations, such as interleukin (IL)-17-producing T (T17) cells, T helper (Th) 1 cells, Th22 cells, Langerhans cells, plasmacytoid DCs, and myeloid DCs. These cells interact with each other then complete psoriasis lesions. Inflammatory myeloid DCs release IL-23 and IL-12 to activate T17 cells, Th1 cells, and Th22 cells, and to produce the cytokines IL-17, interferon-γ, tumor necrosis factor (TNF), and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. Genetic studies also point to the importance of IL-23 in psoriasis pathogenesis. These findings indicate the central role of the IL-23/T17 axis in psoriasis. Our current model for disease pathogenesis emphasizes the central role of IL-23 in controlling activation of lymphocytes that produce IL-17 and a number of emerging therapies for psoriasis are targeted to the IL-23/T17 response axis.