UC San Diego

Atopic dermatitis (AD) is a chronic inflammatory disease, characterized by eczematous lesion (skin inflammation with serous discharge) and excessive pruritus(itching). The early onset, relapsing nature and worsening of scratch- itch symptoms at night results in both patients' restlessness and socioeconomic burden. In addition to the prominent skin symptoms, AD patients are prone to develop allergic rhinitis (nasal allergy) and asthma, through a progressive hypersensitization process called atopic march. Moreover, the impaired skin barrier function in AD patients makes them vulnerable for infection by microbial organisms, which can further exacerbate the inflammation of the skin. Both environmental and genetic factors contribute to development of AD. However the exact cause of this disease is still unknown. Studies aimed at identifying the causes of AD have led to the development of multiple murine models of this disease. Observations of these models have given rise to treatments that ease AD's symptoms, but the lack of a permanent cure and the high ratio of deleterious side effects to symptom suppression necessitate the search for novel pathways that can be targeted for long lasting treatment. We analyzed the epidermis of a new mouse model in which the lack of a functional gene for PLC[Beta]3 leads to spontaneous AD. Upon challenging the skin with extracts of house dust mite, Dermatophagoides farina (Der f), and Staphylococcal enterotoxin B (SEB), mice exhibited early onset AD symptoms. These symptoms appeared more severe in PLC[Beta]3-/- mice compared to their wild-type littermates. By using these inducible AD models, we characterized the impact of immune cells and their downstream effectors on the epidermal phenotypes of atopic dermatitis