Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis

•Dysbiosis drives eczematous dermatitis in Adam17fl/flSox9-Cre mice•Dysbiotic floras sequentially emerge and have differential roles in eczema formation•Dysbiosis is partially dependent on impaired EGFR signaling•Langerhans cells initiate immune response against S. aureus

SummaryStaphylococcus aureus skin colonization is universal in atopic dermatitis and common in cancer patients treated with epidermal growth factor receptor inhibitors. However, the causal relationship of dysbiosis and eczema has yet to be clarified. Herein, we demonstrate that Adam17fl/flSox9-Cre mice, generated to model ADAM17-deficiency in human, developed eczematous dermatitis with naturally occurring dysbiosis, similar to that observed in atopic dermatitis. Corynebacterium mastitidis, S. aureus, and Corynebacterium bovis sequentially emerged during the onset of eczematous dermatitis, and antibiotics specific for these bacterial species almost completely reversed dysbiosis and eliminated skin inflammation. Whereas S. aureus prominently drove eczema formation, C. bovis induced robust T helper 2 cell responses. Langerhans cells were required for eliciting immune responses against S. aureus inoculation. These results characterize differential contributions of dysbiotic flora during eczema formation, and highlight the microbiota-host immunity axis as a possible target for future therapeutics in eczematous dermatitis.

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