Atopic dermatitis is a common skin disease in humans and dogs. It is characterized by a type 2 inflammatory reaction in the skin with accumulation of eosinophils, mast cells and M2 macrophages. It is typically driven by Th2 lymphocytes and associated with an increase of IgE antibodies, but recent studies have demonstrated that innate lymphoid cells also contribute and sometimes are the main instigators of type 2 inflammation. Our initial work focused on a mouse mutant that lacks a protein called SHARPIN. These chronic proliferative dermatitis (cpdm) mice were discovered by us in the early 1990’s. In the absence of SHARPIN, the mice develop a progressive chronic dermatitis with histologic features of atopic dermatitis and an eosinophilic esophagitis at about 4-5 weeks of age. The dermatitis and esophagitis develop in the absence of B and T lymphocytes. We recently developed a floxed Sharpin mutant and demonstrated that selective deletion of Sharpin in keratinocytes recapitulates the dermatitis. Atopic dermatitis is associated with changes in the lipid barrier formed by the stratum corneum. Using a shotgun lipidomics approach, we identified changes in the lipid composition of the epidermis of Sharpincpdm mice. Ongoing studies are aimed at lipid profiling of the epidermis of dogs with atopic dermatitis.
- HogenEsch H, Gijbels MJJ, Offerman E, Van Hooft J, Van Bekkum DW, Zurcher, C (1993) A spontaneous mutation characterized by chronic proliferative dermatitis (cpd) in C57BL/Ka mice. Am J Pathol, 143:972-982.
- Wang Z, Potter CS, Sundberg JP, HogenEsch H (2012) SHARPIN is a key regulator of immune and inflammatory responses. J Cell Mol Med, 16:2271-2279.
- Franco J, Ferreira C, Paschoal Sobreira TJ, Sundberg JP, HogenEsch H (2018) Profiling of epidermal lipids in a mouse model of dermatitis: Identification of potential biomarkers. PLoS One 13: e0196595.