Persistent secretion of IL-18 in the skin contributes to IgE response in mice.

Publisher: [Oxford University Press Country of Publication: England NLM ID: 8916182 Publication Model: Print Cited Medium: Print ISSN: 0953-8178 (Print) Linking ISSN: 09538178 NLM ISO Abbreviation: Int Immunol Subsets: MEDLINE

Original Publication: Oxford : [Oxford University Press, 1989-

Immunoglobulin E/*immunology ; Interleukin-18/*metabolism ; Skin/*metabolism; Animals ; CD4 Antigens/immunology ; Female ; Mice ; Mice, Inbred C57BL ; STAT6 Transcription Factor ; Skin/immunology ; Skin Transplantation/immunology ; Th1 Cells/immunology ; Th2 Cells/immunology ; Trans-Activators/immunology

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.

0 (CD4 Antigens)
0 (Interleukin-18)
0 (STAT6 Transcription Factor)
0 (Stat6 protein, mouse)
0 (Trans-Activators)
37341-29-0 (Immunoglobulin E)

Date Created: 20030417 Date Completed: 20031218 Latest Revision: 20190513

20231215

10.1093/intimm/dxg062

12697661