Figure 1.

Schematic representation of the cytokine network driving development of psoriasis. Cytokines mediate intercellular communication between skin-infiltrating activated immune cells and epidermal keratinocytes. Resident T-cells and antigen-presenting cells are activated upon stimulation by stress or infection (indicated by lightning symbol), leading to production of cytokines, as indicated by horizontal arrow labeled with boxed cytokines. Naïve CD4⁺ T-cells undergo differentiation upon exposure to different cytokine milieus, as indicated by the listed cytokines driving the differentiation into one of five T-helper (T_h) cell lineages, T_h1, T_h2, T_h17, T_h22, or T_reg. A subset of cytokines (listing is not intended to be absolute), produced by each of the T_h lineages and macrophages, orchestrates a multi-faceted stimulation of epidermal keratinocytes. This leads to production of an additional set of cytokines triggering epidermal remodeling through altered keratinocyte growth and differentiation as well as angiogenesis. Numbers in blue ovals above cytokine names indicate the number of AUUUA pentamer sequences (potential ARE sequences) that are located in the 3'UTR of each cytokine mRNA (or for heterodimeric cytokines the number of AUUUA sequences in mRNA species encoding each of the two subunits). Also shown is the development of pre-psoriatic, non-lesional skin (left insert) to a psoriatic plaque (right insert) driven by activated immune cells and cytokine-activated keratinocytes. The lesional skin section shows thickened epidermis with elongated retes and an abnormal outer skin layer (stratum corneum) with formation of epidermal scales. Skin-infiltrating immune cells (including activated T_h cells, dendritic cells, and macrophages) are visible in the dermis.