The Spectrum of Mild to Severe Psoriasis Vulgaris Is Defined by a Common Activation of IL-17 Pathway Genes, but with Key Differences in Immune Regulatory Genes

Overall, skin inflammation, defined as the sum of T-cell infiltration/activation and IL-17-mediated epidermal responses, was not higher in severe psoriasis lesions. Surprisingly, mild psoriasis was characterized by higher numbers of T cells in skin lesions, higher IL-17A expression, and stronger expression of the core psoriasis transcriptome. In contrast, severe psoriasis was characterized by stronger expression of some epidermal response genes (TGFA, CALM1, SMPD3, and IL1RL2). However, a key molecular distinction was higher expression of negative immune regulatory genes (CTLA4, CD69 and PD-L1) in mild lesions compared with severe psoriasis lesions. These data have important implications for treating psoriasis across the spectrum of disease, as well as for potential mechanisms that allow psoriasis to progress to more extensive cutaneous disease.