Expression and activity of IL-17 receptor subunits in human cutaneous cells as targets for anti-IL-17 therapeutic antibodies.

The key players in different chronic inflammatory skin diseases are cytokines belonging to the IL-17 group, IL-17 receptors and a T helper cell population, Th17 cells. Successful therapeutic strategies that target either IL-17 or the major IL-17 receptor IL-17RA have confirmed the immune-pathogenic pathway. To study the IL-17-ligand - receptor axis at the molecular level, a number of cutaneous cell types from healthy human subjects has been cultured and analyzed for the expression of IL-17 receptors. IL-17RA was the most abundantly expressed receptor type in keratinocytes, epidermal stem cells, fibroblasts, mesenchymal stem cells, hemo- and lymphovascular endothelial cells. IL-17RC and IL-17RD showed moderate expression, while the genes for IL-17RB and IL-17RE were poorly expressed. In none of the investigated cell types, IL-17 ligands caused an increased expression level of the five receptor types in time- and dose-dependent experiments. No evidence for IL-17A, -C, -E or -F induced signal transduction cascades could be obtained by a qRT-PCR and western blot analyses. Further studies are necessary to identify relevant co-stimulating factors from IL-17 subtypes under physiological and pathophysiological conditions.