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

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 (α_E subunit)-expressing CD4⁺ T lymphocytes. However, the absence of CD103 on approximately 50% of infiltrating cells argues against a primary role for the α_Eβ₇ 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

Acknowledgments

We thank Dr Michelle Lin and Cliff Rims for technical assistance. This work was supported by a Dermatology Foundation Career Development Award (JY) and NIH grants AR051683 (JY), HL082658 (WCP), HL089455 (WCP).

Disclosure

The authors report no conflicts of interest in this work.