Head and Neck Radiotherapy Induces a Transcriptional Profile Associated with Inflammation and Damage

Oral Mucositis (OM) is a deleterious side effect of radiotherapy targeting the head and neck. OM is characterized by tissue injury to the oral cavity and the severe ulcers that form can result in increased hospitalizations and cessation of cancer treatment. Approximately 80% of patients undergoing radiotherapy for head and neck malignancies develop OM, representing a major unmet medical condition. Our understanding of immunopathogenesis of OM is limited and this leads to a lack of effective therapies without deleterious side effects. In order to develop better therapeutics, an understanding of the pathophysiology of OM is necessary. To understand key mediators during peak damage of OM we performed RNA-sequencing to view the whole transcriptome of murine tongue tissue. RNA-sequencing is a technique which utilizes Next Generation Sequencing (NGS) to view all of the RNA in a given sample at a particular time. This technique lends the ability to assess transcriptional changes and understand gene expression. The goal of this thesis was to identify the transcriptional profile induced in head and neck irradiated tongue tissue via high throughput sequencing. In general, the pathogenesis of OM is similar between mice and humans making this study valuable in improving our understanding of key players during OM. Utilizing toluidine blue staining, we found 99% of damage post radiotherapy to be localized to the distal portion of murine tongue tissue so sequencing profiles of the proximal and distal segments were analyzed. RNA-sequencing of murine tongue tissue showed elevated expression of IL-17 and related immune pathways in response to head and neck radiotherapy. Interleukin-17 (IL-17) is a pro-inflammatory cytokine that is both protective and pathogenic depending on disease context. Since IL-17 has a convoluted role in mucosal immunity a better understanding of its function in OM is required. Clarification of IL-17 in OM could lead to the development of novel therapeutics.