536 Staphylococcus aureus proteases trigger skin inflammation via eosinophil-derived IL-17 responses

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disorder that affects 25% of children 7-10% adults an associated $5.2 billion in annual healthcare costs the U.S. Although precise etiology AD unclear, it with complex interaction epidermal barrier defects, abundant S. aureus colonization, immune dysregulation, including eosinophilic infiltrate correlates disease severity. However, role eosinophils pathogenesis largely undefined. To address this gap knowledge, we used vivo epicutaneous mouse model which aureus-soaked gauze pad was applied to back for 7 days wildtype (WT) eosinophil-deficient mice, performed image, histologic, flow cytometric, RNAseq analyses. We discovered mice had reduced inflammation correlated decreased IL-17 pathway gene expression compared WT mice. determine skin, IL-17A-tdTomato/IL-17F-GFP dual reporter found were predominant expressing cells inflamed skin. Furthermore, adoptive transfer into IL-17A/F deficient restored inflammation, but not presence neutralizing antibodies. This relevant humans, as patient significantly increased IL-17-expressing healthy Lastly, proteases crucial recruitment producing eosinophils. Taken together, uncovered novel mechanism whereby trigger via eosinophil-derived responses, has implications development immune-based therapies against potentially other diseases.