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Atopic dermatitis (AD) is a common inflammatory skin disease of unknown etiology. Cutaneous infection with microbes such as Staphylococcus aureus and/or skin cleansing with detergent exacerbates clinical AD. Here, we generated an AD animal model by destroying skin barrier function with detergent and subsequent topical application of protein A from S. aureus (SPA). NC/Nga mice, which genetically have reduced skin barrier function, and BALB/c mice having intact skin barrier function, were susceptible to this combination and developed severe and moderate AD, respectively, associated with dermal accumulation of eosinophils and mast cells. Both types of mice showed an increase in serum levels of IL-18, but not IgE. The epidermis of the NC/Nga mice rapidly expressed T helper type 1 (Th1)-associated chemokines, including ligands for CXCR3 and CCRS, after application of both SpA and detergent, but not after application of detergent alone. Although treatment with detergent induced moderate Th1 cell response, additional SpA treatment was a prerequisite for induction of the differentiation of naive T cells toward unique Th1 cells, termed 'super Th1 cells,'' capable of producing both Th1 (IFN-[gamma],) and T helper type 2 cytokine (IL-13), as well as IL-3, and expressing CXCR3 and CCR5. Induction of super Th1 cells required IL-18 stimulation. Blockade of IL-18 prevented AD development, whereas blockade of IL-3 partially prevented AD development, suggesting a contribution of IL-18-dependent IL-3 production to AD with cutaneous mastocytosis. il[18.sup.-/-]BALB/c mice similarly evaded SDS/SpA-induced AD. Thus, IL-18 might be important for the development of infectionassociated AD by induction of IL-3 from super Th1 cells. IL-3 | protein A r IFN-[gamma] | super Th1 cells | intrinsic atopic dermatitis

Transgenic mice expressing the mouse interleukin 33 (IL-33) gene driven by a keratin 14 promoter were generated. The skin-selective expression of the IL-33 gene was enhanced, and intense immunofluorescence for IL-33 was evident in the nuclei of the epidermis. Spontaneous itchy dermatitis developed in those mice at 6-8 wk of age in specific pathogen-free conditions. In the lesional skin, the epidermis was thickened and the eosinophils were infiltrated with increased expression of the eosinophil peroxidase and major basic protein genes. Mast cells were also abundant there, and blood histamine and total IgE levels were high. Those phenotypes closely resemble the features of atopic dermatitis. In peripheral blood and lesional skin, IL-5, IL-13, regulated upon activation, normally T-expressed, and presumably secreted (RANTES)/CCL5, and Eotaxin 1/CCL11 were increased, whereas TNF-α, IFN-γ, and thymic stromal lymphopoietin (TSLP) were unaltered. Furthermore, the proportion of group 2 innate lymphoid cells (ILC2s), which produce IL-5, were significantly increased in the lesional skin, peripheral blood, and regional lymph nodes. The dermatitis with eosinophil infiltration was improved by the administration of an anti-IL-5 antibody. These results suggest that the expression of IL-33 in the skin activates an immune response involving ILC2 and that this process might play a crucial role in the pathogenesis of allergic inflammation that is characteristic of atopic dermatitis. [ABSTRACT FROM AUTHOR]

When animals are infected with helminthic parasites, resistant hosts show type II helper T immune responses to expel worms. Recently, natural helper (NH) cells or nuocytes, newly identified type II innate lymphoid cells, are shown to express ST2 (IL-33 receptor) and produce IL-5 and IL-13 when stimulated with IL-33. Here we show the relevant roles of endogenous IL-33 for Strongyloides venezuelensis infection-induced lung eosinophilic inflammation by using Il33(-/-) mice. Alveolar epithelial type II cells (ATII) express IL-33 in their nucleus. Infection with S. venezuelensis or intranasal administration of chitin increases in the number of ATII cells and the level of IL-33. S. venezuelensis infection induces pulmonary accumulation of NH cells, which, after being stimulated with IL-33, proliferate and produce IL-5 and IL-13. Furthermore, S. venezuelensis infected Rag2(-/-) mice increase the number of ATII cells, NH cells, and eosinophils and the expression of IL-33 in their lungs. Finally, IL-33-stimulated NH cells induce lung eosinophilic inflammation and might aid to expel infected worms in the lungs.