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Also, current mouse models reflect human AD only unsatisfactorily. Therefore, we have asked whether a humanized AD mouse model can be developed that reflects human AD more faithfully and permit to identify key signals that suffice to induce AD lesions in previously healthy human skin in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Healthy human skin from non\u2010atopic donors was transplanted onto SCID\/beige mice. After xenotransplant reinnervation by mouse sensory nerve fibers had occurred, mixed autologous human Th2 CD4+ and Tc2 CD8+ T cells that had been pretreated in vitro with IL\u20102, IL\u20104, and LPS were injected intradermally into the xenotransplants without skin barrier disruption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Injected non\u2010atopic xenotransplants rapidly developed a morphological, functional, and immunological phenocopy of human AD lesions regarding skin barrier defects, immunopathology including intraepidermal eosinophils, mast cell activation, increase of thymic stromal lymphopoietin, eotaxin\u20101 and type 2 cytokine circuits, and even showed characteristic neuroimmunological abnormalities such as \u00df2\u2010adrenergic receptor downregulation. The experimentally induced AD lesions in human skin responded to standard AD therapy (topical dexamethasone or tacrolimus; systemic anti\u2010IL\u20104R\u03b1 antibody [dupilumab]), and relapsed when neurogenic skin inflammation was induced by exposing mice to perceived stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This new animal model uniquely mimics the complexity of human AD and its clinical response to standard therapy and psychoemotional stressors in vivo, and shows that Th2\u2010polarized lymphocytes associated with excessive IL\u20104R\u03b1\u2010mediated signaling suffice to induce human AD skin lesions, while atopy and epidermal barrier disruption are dispensable.<\/jats:p>\n                  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