323 A Novel, Stress-Responsive and Clinically Predictive Humanized Mouse Model of Atopic Dermatitis: Autologous Th2-Polarized Lymphocytes Suffice to Induce Characteristic Lesions in Healthy Non-Atopic Human Skin Xenotransplants In Vivo

Abstract

Clinically relevant in vivo models for atopic dermatitis (AD) are needed, in which the minimal signals required for AD induction in human skin can be defined and candidate therapeutics explored. Here, we report a novel humanized AD mouse model that uses split-thickness skin from healthy, non-atopic female human donors xenotransplanted onto SCID/beige mice and injected with autologous, Th2-polarized PBMCs. After intradermal injection of PBMCs preincubated only with IL-2, IL-4 and LPS, the xenotransplants develop a phenocopy of human AD lesions, including epidermal hyperplasia, hyperproliferation, erythema, and skin barrier impairment (reduced filaggrin and claudin-1 expression, altered corneocyte nanotexture [atomic force miocroscopy]).