Abstract
Atopic dermatitis (AD) is the initial step of the atopic march: the progression from AD to allergic rhinitis and asthma. There is a close association between skin barrier abnormalities and the development of AD and the atopic march. One of cardinal features of AD is that the lesional skin of the majority of AD patients is chronically colonized with Staphylococcus aureus with half isolates producing superantigen enterotoxin B (SEB). Although diverse roles of SEB in the pathogenesis and severity of AD have been recognized, whether SEB contributes to the dermal inflammation that drives lung inflammation and airway hyperresponsiveness (AHR) has not been examined. Here we show a novel role of S. aureus superantigen SEB in augmenting allergen ovalbumin (Ova) induced atopic march through an IL-17A dependent mechanism. When mice epicutaneously (EC) sensitized with allergen Ova, addition of topical SEB led to not only augmented systemic Th2 responses but also a markedly exaggerated systemic Th17/IL-17 immune environment. The ability of SEB in enhancing Th17/IL-17 was mediated through stimulating lymphocytes in spleen and draining lymph nodes to promote IL-6 production. Epicutaneous sensitization of mice with a combination of Ova and SEB significantly enhanced Ova-induced AHR and granulocytic lung inflammation than Ova allergen alone. When IL-17A was deleted genetically, the effects of SEB on augmenting lung inflammation and AHR were markedly diminished. These findings suggest that chronic heavy colonization of enterotoxin producing S. aureus in the skin of patients with atopic dermatitis may have an important role in the development of atopic march via an IL-17A dependent mechanism.
Highlights
The hallmarks of atopic dermatitis (AD), termed atopic eczema, include chronic, pruritic, relapsing form of skin inflammation, disturbance of epidermal-barrier function that culminates in dry skin, and IgE-mediated sensitization to environmental allergens [1]
It has been shown that topical superantigen enterotoxin B (SEB) superantigen exposure in the skin induces mixed T-helper 1 (Th1)/Th2 type dermatitis and production of IgE antibodies in a murine model of atopic dermatitis in wild type mice on BALB/c genetic background [30]
We showed that epicutaneous immunization of mice with a combination of Ova and SEB exhibited significantly enhanced skin inflammation, IL-17A than Ova-sensitization alone, suggesting that SEB contributes to Ovainduced Atopic dermatitis (AD)
Summary
The hallmarks of atopic dermatitis (AD), termed atopic eczema, include chronic, pruritic, relapsing form of skin inflammation, disturbance of epidermal-barrier function that culminates in dry skin, and IgE-mediated sensitization to environmental allergens [1]. The concept of a progressive atopic march is supported by multiple lines of genetic, epidemiological and experimental evidence. These studies indicate that reduced filaggrin expression in the human skin leading to impaired epidermal barrier function can be a major predisposing factor for AD and subsequent development of the atopic march [8,9,10]. The progression from AD to asthma was supported by experimental data showing that allergen exposure through the epidermis can initiate systemic allergy [16] These data suggest a causal link between childhood eczema and the lateronset respiratory allergic disorders. The underlying mechanisms of the atopic march are largely unknown
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