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• W3090758894 abstract "<h3>Background</h3> <i>Staphylococcus aureus</i> is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in patients with AD is unclear. <h3>Objective</h3> We sought to identify the <i>S aureus</i>–derived virulence factor(s) that initiates the cutaneous type 2–promoting immune response responsible for AD. <h3>Methods</h3> <i>In vitro</i> human keratinocyte cell culture, <i>ex vivo</i> human skin organ explants, and the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse were used as model systems to assess type 2–promoting immune responses to <i>S aureus</i>. Identification of the bioactive factor was accomplished using fast protein liquid chromatography and mass spectrometry. Bioactivity was confirmed by cloning and expression in an <i>Escherichia coli</i> vector system, and <i>S aureus</i> second immunoglobulin-binding protein (Sbi) mutant strains confirming loss of activity. <h3>Results</h3> <i>S aureus</i> was unique among staphylococcal species in its ability to induce the rapid release of constitutive IL-33 from human keratinocytes independent of the Toll-like receptor pathway. Using the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse model, we showed that IL-33 was essential for inducing the immune response to <i>S aureus in vivo</i>. By fractionation and candidate testing, we identified Sbi as the predominant staphylococcus-derived virulence factor that directly drives IL-33 release from human keratinocytes. Immunohistology of skin demonstrated that corneodesmosin, a component of corneodesmosomes that form key intercellular adhesive structures in the stratum corneum, was disrupted, resulting in reduction of skin barrier function. <h3>Conclusions</h3> <i>S aureus</i>–derived Sbi is a unique type 2–promoting virulence factor capable of initiating the type 2–promoting cytokine activity underlying AD." @default.
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• W3090758894 date "2021-04-01" @default.
• W3090758894 modified "2023-10-10" @default.
• W3090758894 title "Staphylococcus aureus second immunoglobulin-binding protein drives atopic dermatitis via IL-33" @default.
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• W3090758894 doi "https://doi.org/10.1016/j.jaci.2020.09.023" @default.
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