systemic sensitization with the protein allergen ovalbumin augments local sensitization in atopic dermatitis

Jane Yoo,1 Anne M Manicone,2 John K McGuire,3 Ying Wang,2 William C Parks2 1Center for Lung Biology, Department of Medicine, Division of Dermatology, 2Division of Pulmonary and Critical Care Medicine, 3Department of Pediatrics, Division Critical Care Medicine, University of Washington, Seattle, WA, USA Abstract: Mouse models of atopic dermatitis based on epicutaneous sensitization have shed light on the role of epicutaneous allergen entry in the development of respiratory and gastrointestinal allergy. However, the contribution of non-cutaneous modes of sensitization to skin diseases has not been evaluated. We assessed if systemic ovalbumin administration, in conjunction with local sensitization, could prime for a robust inflammatory response. Furthermore, we attempted to elucidate important aspects of disease pathogenesis previously unaddressed in mouse models. Mice that underwent intraperitoneal ovalbumin sensitization prior to epicutaneous challenge demonstrated an acute (Th2-polarized) atopic dermatitis-like phenotype upon local challenge. The inflammatory response was strikingly more robust than in mice that underwent epicutaneous sensitization alone. The lesional infiltrate contained a dendritic cell population that corresponded phenotypically with inflammatory dendritic epidermal cells of significance in human disease. Finally, in accordance with observations in human atopic dermatitis, there was an increase in cluster of differentiation (CD) 103 (αE subunit)-expressing CD4+ T lymphocytes. However, the absence of CD103 on approximately 50% of infiltrating cells argues against a primary role for the αEβ7 integrin in tissue homing. In conclusion, we present a mouse model of atopic dermatitis that reveals novel insights into the pathogenesis of this complex disease. Keywords: atopic dermatitis, mouse model, ovalbumin, sensitization, Th2, dendritic cells