A novel role for the TRAIL signalling pathway in the pathogenesis of Eosinophilic Oesophagitis

Eosinophilic Oesophagitis (EoE) is an allergen mediated disorder of the oesophagus, associated with eosinophilic infiltration of the oesophageal epithelial layer and remodelling of oesophageal scaffolding. There has been a significant rise in EoE prevalence over the past ten years, however, therapeutic strategies to counter hallmark EoE features have remained relatively unchanged from steroid therapy and dietary restrictions. The apoptotic factor TRAIL has previously been implicated in allergic asthma as a driver for immune cell infiltration, remodelling and airway hyperreactivity. The upregulation of TRAIL through allergen exposure results in the induction of MID-1 and subsequent downregulation of PP2A: a negative regulator of NF-κB and MAP kinase inflammatory pathways. Given the similarities between EoE and asthmatic inflammation, this thesis will explore the role of the TRAIL signalling pathway through the analysis of EoE oesophageal human biopsies and the employment of EoE in vivo models.