Date of Award
College of Arts & Sciences
The prevalence of asthma and other allergic diseases has increased significantly in the last 30 years (Romagnani, 2004). One of the proposed mechanisms for this trend posits that an over-emphasis on hygiene and increased use of antibiotics results in decreased exposure to bacteria during the early years of life which leads to increased risk of allergic disease (Romagnani, 2004). This is referred to as the “Hygiene Hypothesis”. One of the allergic diseases that is on the rise is atopic dermatitis (AD). AD is an allergic inflammatory skin disease that affects over 17% of children in the United States (Spergel and Paller, 2003). We have generated a mouse model of AD that lacks Notch signaling in the skin. These mice show many of the hallmarks of AD including skin inflammation, systemic allergic bias, and an increased susceptibility to asthma (Demehri et al., 2009). To assess the role that bacteria play in altering the severity of the atopic response, we re-derived our Notch signaling-deficient mice into a germ free facility. The Notch signaling-deficient germ free (GF) mice showed an increased and more variable level of cytokines associated with allergic inflammation and a higher bias towards Th2 cells compared to their conventionally-raised (CR) counterparts. However, these mice did not develop higher serum IgE levels or a significantly more severe skin inflammation. In addition, GF animals responded to asthma challenges similarly to their CR counterparts. Based on these findings, we conclude that although lack of bacteria leads to a more pronounced Th2 bias in mice with Notch-deficient skin, this bias does not translate to more severe symptoms of allergic disease.
Yockey, Laura, "Testing the Hygiene Hypothesis: The Role of Bacteria in Promoting Atopy in a Mouse Model of Atopic Dermatitis" (2011). Undergraduate Theses—Restricted. 1.