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-specific inflammation 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-1beta. 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-1beta, induced long-lasting IgE production in wild-type mice without elevation of circulating IL-18 and IL-1beta. Furthermore, IL-18R-, CD4- or stat6-deficient 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 purified 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.
Nakano
Hiroki
H
Department of Immunology & Medical Zoology, Second Department of Surgery, Hyogo College of Medicine, Nishinomiya 663-8501, Japan. nakaken@hyo-med.ac.jp
Tsutsui
Hiroko
H
Terada
Makoto
M
Yasuda
Koubun
K
Matsui
Kiyoshi
K
Yumikura-Futatsugi
Shizue
S
Yamanaka
Kei-Ichi
K
Mizutani
Hitoshi
H
Yamamura
Takehira
T
Nakanishi
Kenji
K
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology*; D020382:Interleukin-18 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D050800:STAT6 Transcription Factor; D012867:Skin / Q000276:immunology / Q000378:metabolism*; D016038:Skin Transplantation / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000276:immunology
D015704:CD4 Antigens; D020382:Interleukin-18; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D007073:Immunoglobulin E