doi: 10.1093/intimm/dxg062 Persistent secretion of IL-18 in the skin contributes to IgE response in mice

After exposure of the skin to microbes, the host develops skin-speci®c in¯ammation and an acquired immune response, in which keratinocytes (KC) and Langerhans cells play critical roles respectively. We established two animal models. (i) We examined the importance of KC-derived IL-18 for the systemic IgE response by using a skin transplantation model. As previously reported, transgenic mice (KCASP1Tg), that over-express caspase-1 in their KC, display high serum levels of IgE, and spontaneously develop chronic dermatitis by production of IL-18 and IL-1b. We examined the capacity of transplantation of cutaneous lesions from KCASP1Tg to induce IgE production in wild-type or mutant mice with a syngeneic background. Transplantation of active cutaneous lesions, that expressed high levels of IL-18 and IL-1b, induced long-lasting IgE production in wild-type mice without elevation of circulating IL-18 and IL-1b. Furthermore, IL-18R-, CD4- or stat6-de®cient mice transplanted with the lesions did not produce IgE, indicating that this IgE response is initiated by IL-18, and dependent on host-derived CD4+ T cells and stat6. (ii) We investigated IL-18 secretion from KC upon stimulation with microbe products. Freshly isolated KC from wild-type mice secreted IL-18 in response to Protein A puri®ed from Cowan 1 strain of Staphylococcus aureus (SpA), which often exacerbates human skin diseases, including atopic dermatitis. Cutaneous application of SpA increased serum levels of IL-18 and IgE. These results indicate that local accumulation of IL-18 triggers systemic IgE responses without exposure to antigen