The staphylococcal protease SspA perturbs the epidermal barrier and promotes IL-22-driven inflammation in allergen-exposed skin.

SspA, a serine protease from Staphylococcus aureus, destroys keratinocyte junctions, increases epidermal permeability, and activates an epithelial inflammatory program linked to barrier dysfunction.

• Why it matters: Skin colonization by Staphylococcus aureus is common in atopic dermatitis and allergic diseases, but its mechanism for driving inflammation and pathology is unclear.
• What they did: Using S. aureus secretome analysis and bioactivity-guided fractionation, the study identified SspA activity on keratinocyte junctions and barrier function, then tested epicutaneous SspA plus HDM in mice.
• The result: In mice, SspA-HDM induces IL-22-dependent atopic dermatitis-like disease with IL-13/IL-22–producing T cells and epidermal nerve fiber changes, and chemical denervation reverses the neuroimmune network–linked pathology.