361 Skin-induced IL-36 triggers plasma cell IgE class switching and allergic disease

Abstract

Atopic dermatitis (AD) is an inflammatory, relapsing, itchy skin disorder that affects 15-30% of children and up to 5% of adults. AD patients exhibit elevated serum IgE and Staphylococcus aureus colonization on lesional skin that correlates with disease severity. We previously discovered that S. aureus induces IL-36-dependent AD-like skin inflammation. However, it is unclear what role S. aureus has on allergic IgE responses. Herein, we used a S. aureus epicutaneous infection model to mimic AD skin inflammation and examine the immune mechanisms of IgE production. Interestingly, epicutaneous S. aureus infection promoted IL-36-dependent IgE responses and plasma cell populations. Treatment with an anti-mouse IL-36R mAb decreased both skin inflammation and IgE levels. B cells stimulated in vitro with rIL-36α showed enhanced IgE expression and plasma cell differentiation compared to rIL-4 stimulation alone. To examine the role of S. aureus-induced IgE on secondary allergic lung inflammation, mice were co-sensitized with epicutaneous S. aureus and cockroach antigen (CRE), followed by CRE intratracheal lung challenge. Mice co-sensitized with S. aureus and CRE demonstrated significantly increased weight loss, lung pathology, and bronchoalveolar lavage IgE levels when compared to mice sensitized with either S. aureus or CRE alone. Additionally, IL-36R -/- mice exhibited significantly decreased weight loss compared to wild type mice, suggesting skin-derived IL-36 can influence secondary allergic disease. Taken together, these data demonstrate that epicutaneous S. aureus can mediate IgE responses via IL-36 signaling, and present a potential therapeutic for AD and other allergic diseases.