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• W4366185764 abstract "Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. House dust mite (HDM), a common aeroallergen associated with AD, is increasingly employed in mouse models as a pharmacology platform to evaluate novel AD targets. In the current study, we compared the AD-like phenotypes between two mouse strains, NC/Nga and BALB/c, in response to repeated applications of Dermatophagoides farinae extract (Biostir AD ointment). In-life endpoints were measured including skin clinical scores, transepithelial water loss (TEWL), scratching bouts, as well as terminal endpoints (total serum IgE and tissue cytokines). Six applications of Biostir AD (twice/week) to back and ears resulted in moderate to severe dermatitis in NC/Nga as evidenced by significant increases in clinical scores, scratching bouts, and TEWL. In contrast, BALB/c showed mild skin lesions with only a trend of increase in scratching bouts and TEWL, but higher serum total IgE. Increases of inflammatory cytokines IL-4, IL-13, IL-31, TNF-α, IL-1β, IL-17A, and TARC in ear and back skin were significantly greater in NC/Nga. Further phenotyping of NC/Nga was performed, including histology, flow cytometry, and pharmacology. Significant acanthosis, spongiosis, parakeratosis, and increased eosinophil infiltrate were observed in lesional NC/Nga skin. Flow cytometry of skin revealed a mixed immune response with increased IL-4, IL-13, IL-17A and IFNγ from CD3+CD4+ T cells, CD3+CD8+ T cells, and CD3negcells. JAK1 inhibitor and IL-4R antibody dose-dependently inhibited multiple AD-like endpoints in NC/Nga mice. Together these data confirm NC/Nga are predisposed to HDM-induced dermatitis compared to BALB/c, and the immune profile is complex, including innate and adaptive responses. Further studies are needed to enhance our understanding of HDM-induced immune responses in this model and to evaluate its utility in drug discovery for AD." @default.
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• W4366185764 date "2023-05-01" @default.
• W4366185764 modified "2023-09-28" @default.
• W4366185764 title "1080 Biostir AD ointment induces a stronger atopic dermatitis-like phenotype in NC/Nga mice than BALB/c mice" @default.
• W4366185764 doi "https://doi.org/10.1016/j.jid.2023.03.1092" @default.
• W4366185764 hasPublicationYear "2023" @default.
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