A study for atopic dermatitis controlledby Caspase-1 and IL-18

我们建立了两只转基因小鼠（皮肤特异性caspase-1和IL-18过表达小鼠），这些小鼠出现了类似于人类特应性皮炎（AD）的持续性皮炎。这些小鼠的皮肤和全身免疫系统过敏型转移到Th2状态，分泌IL-18、IL-4、IL-5和IL-10。皮肤肥大细胞增多症和高组胺血症导致强烈的抓挠行为，作为特应性皮炎的特征模型，血清IgE水平显著升高。IgE-/- caspase - 1tg使AD型皮损持续存在，但IL-18的消除完全抑制了皮损的发展，这有力地支持了这种皮炎对IL-18的依赖性。由于这些病变与外源性过敏原无关，我们提出了一个新的概念，即先天型特应性，而不是过敏原依赖性IgE介导的特应性。我们成功地使用卡介苗接种抑制IL-18产生的caspase-1Tg的皮肤表现。我们还开发了Stat6-/-caspase- 1tg，其皮肤病变类似于脓疱性牛皮癣，但没有Th2移位。这些研究揭示了经皮il -18分泌在Th2型AD和Th1型牛皮癣中的重要性。

We have established two transgenic mice (skin specifically caspase-1 and IL-18 overexpressed mice), and these mice developed persistent dermatitis similar to the human atopic dermatitis (AD). The skin and systemic immune systems of these mice were allergic type shifted to Th2 conditions, secreting IL-18, IL-4, IL-5 and IL-10. Dermal mastocytosis and hyper histaminemia resulted in intensive scratching behaviour as a characteristic model for atopic dermatitis, and significant elevation of serum IgE levels. IgE-/-Caspase-1Tg persisted AD type skin lesions, but extermination of IL-18 completely suppressed development of the skin lesions, which strongly supported IL-18 dependency of this dermatitis. Because these lesions were independent from the exogenous allergens, we proposed a new concept as innate type atopy in contrast to the allergen dependent IgE mediated atopy. We successfully treated the skin manifestations of the caspase-1Tg using BCG vaccination with suppressed IL-18 production. We also developed Stat6-/-caspase-1Tg, which developed skin lesions mimic pustular psoriasis without Th2 shift. These studies revealed importance of the percutaneous IL-18secretion in both of Th2 type AD and Th1 type psoriasis.