Primary human keratinocytes efficiently induce IL-1-dependent IL-17 in CCR6+ T cells

Keratinocytes and activated T cells interact in skin inflammation by virtue of chemokines and cytokines. T cell-derived IL-17 has been described to play an important role in the course of psoriatic inflammation. In this study, we addressed how keratinocytes influence the secretion of IL-17 in autologous T cell subsets. We found that a co-culture of autologous keratinocytes and T cell-receptor-stimulated T cells markedly enhanced the production of IL-17. Besides the importance of direct cell contact, this effect was mainly mediated by IL-1 and could be blocked by the IL-1 antagonist anakinra. An additional increase in IL-17 production by IL-23 was only seen in the presence of IL-1, which thus plays a permissive role for the action of IL-23. Importantly, co-culture of keratinocytes with CCR6+ CD4+ T cells that are enriched for Th17 cells resulted in significantly higher IL-17 production compared to co-culture with CD4+ T cells.