Human keratinocytes respond to interleukin-18: implication for the course of chronic inflammatory skin diseases

Abstract

Interleukin (IL)-18 has been described to play a role in several inflammatory skin diseases such as eczema and psoriasis. In this study, we aimed to elucidate keratinocytes as potential targets for IL-18 effects. In human primary keratinocytes expression of IL-18Ralpha as well as responses to IL-18 were determined. In keratinocytes freshly isolated from skin biopsies of lesional atopic dermatitis or psoriasis, we observed a significantly higher expression of the IL-18Ralpha as compared with keratinocytes from normal donors. A marked upregulation was induced in vitro upon stimulation with interferon (IFN)gamma+tumor necrosis factor (TNF)alpha or poly I:C. IL-4 led to downregulation of IL-18Ralpha. IL-18-induced CXCL10/IP-10 production in freshly isolated keratinocytes from lesional psoriasis as well as in cultured normal keratinocytes. Furthermore, IL-18 upregulated major histocompatibility complex (MHC) class II expression on IFNgamma-stimulated keratinocytes. This was of functional significance as verified in coculture experiments with CD4+ T cells in the presence of superantigen. T cells produced significant amounts of IFNgamma after coculture with IL-18-induced MHC class II expressing keratinocytes. In conclusion, we have shown that keratinocytes functionally respond to IL-18 with upregulation of MHC II and production of the chemokine CXCL10/IP-10. These findings further support an important role of IL-18 in inflammatory skin diseases in the epidermal compartment.