Graduation Date

Spring 5-5-2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Medical Anatomy

Abstract

Eosinophilic Esophagitis (EE) is a chronic inflammatory disease that effects individuals of all ages. EE is mediated by an allergen response, causing the release of thymic stromal lymphopoietin (TSLP), and subsequent inflammation and eosinophil migration and infiltration of the esophagus through the activation of the JAK/STAT pathway and CD4+ T-cells. EE has typically been associated with food allergies, but studies have shown that aeroallergens can cause EE as well. Current treatments of EE have primarily focused on nonspecific methods, though anti-TSLP is beginning to be tested as a possible treatment for EE. The aim of this study was to see how house dust mites affected tight junction function in esophageal cells and determine if application of anti-TSLP will prevent dust mite’s effects. This was accomplished through a transwell cell culture model. Dust mites along with experimental conditions Gö 6976, interferon-gamma, eosinophils, and TSLP synthetic peptide (anti-TSLP) was used to determine how these conditions affected esophageal cell tight junctions. Transepithelial electrical resistance (TEER) was recorded to measure epithelial integrity. Cells were analyzed through Prism and imaged by immunofluorescence staining. Results showed that dust mites caused a decrease in epithelial resistance through a 24-hour period. Interactions between eosinophils and dust mites caused further decreases in epithelium resistance. When esophageal cells are treated with anti-TSLP, the addition of dust mites did not cause a fall in electrical resistance; however, it did not stop eosinophils disruption of epithelial resistance. Immunofluorescence was used to show changes in tight junction function for each condition. These findings indicate that dust mites do affect esophageal cell function and anti-TSLP negates the disruptive actions of dust mites. Further studies have to be conducted to understand aeroallergens role in EE and how treatments can be tailored for aeroallergens.

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