Grant: Doctoral Research Award - PA: Digestive Health (SHOPP)

The esophagus, once considered merely a conduit for food entering the digestive system, is now known to also act as an sentry organ for the immune system. How the esophagus senses and reacts to foreign microbes and the subsequent manifestation of esophageal inflammation ('esophagitis') is a poorly understood, complex and clinically relevant issue. In general, the immune system employs two strategies for protection: recognition of molecular patterns of foreign invaders and adaptation to previously encountered infectious agents. It is likely that both of these are ongoing processes in the esophagus. Adaptation to infectious agents occurs by presentation of pieces of infectious chemicals (antigen) by body cells to immune sentry cells present in all tissues. This process is known as antigen presentation, a well-described phenomenon in many parts of the body, and may occur in the esophagus. In this project, the possibility of antigen presentation in the esophagus will be investigated (Objective 1) and the ability of antigen presentation to initiate inflammation will be described (Objective 2). Immune recognition of molecular patterns is primarily mediated by pattern recognition receptors (PRRs). PRRs are known to be present on many types of cells, such as the cells lining the intestine and the bladder. This study will investigate the possibility that resident cells lining the esophagus express PRRs. The function of PRRs as detectors of microbial invasion into the digestive tract will be systematically described and their contribution to inflammation assessed (Objective 3). Based on the mechanisms of PRR signaling and antigen presentation discovered, specific PRR and antigen presenting antagonists will be investigated (Objective 4). In summary, this thesis will characterize the mechanisms that may initiate inflammation in the esophagus, with the ultimate aim of developing effective therapies for the treatment of esophagitis by blocking these processes.