| Budget Amount *help |
¥61,000,000 (Direct Cost: ¥61,000,000)
Fiscal Year 2005: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2004: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2002: ¥16,000,000 (Direct Cost: ¥16,000,000)
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| Research Abstract |
We previously showed that transgenic mice that over-secrete IL-18 from their epidermal cells spontaneously develop AD-like dermatitis independently of Th2 or IgE response. Furthermore, recent clinical studies revealed that serum levels of IL-18 well parallel with the disease severity of AD. Therefore, we assumed that endogenous IL-18 contributes to the development of AD, particularly intrinsic AD. It is well documented that cutaneous infection with Staphylococcus aureus exacerbates clinical AD. Recently, we demonstrated that S. aureus -derived proteinA (SpA) induces IL-18 release from skin. Here, we generated a novel intrinsic AD mouse model by daily topical application of SpA following destroying skin barrier by detergent (SDS). AD-prone NC/Nga mice showed 100% development of AD and manifested skin phenotypes with dense accumulation of leukocytes including mast cells. They exhibited elevated serum levels of IL-18 but not IgE. After application of NC/Nga mice with SpA/SDS, CD4^+ T cells prepared from their regional lymph nodes produced IFN-γ, IL-3, IL-9 and IL-13. As they produce both Th1- and Th2-cytokines, we proposed to designate them super Th1 cell. Importantly, we found that IL-18 or IL-3 blockade, completely and partly, prevented the AD development by inhibiting this T cell differentiation or the mast cell accumulation, respectively. Thus, IL-18 might be a novel target for the treatment of infection-associated AD.
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