Immunological mechanisms of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic allergen-driven disease that is characterized clinically by symptoms of esophageal dysfunction, and histologically by eosinophil-dense inflammation in the esophagus. EoE incidence has rapidly increased since its first description in 1994. Patient quality of life is severely impacted by symptoms, which include dysphagia and food impaction. Current treatment options involve dietary restrictions, topical corticosteroids and more recently also biologicals, but (long-term) effectiveness varies. Therefore, it is of great importance to elucidate underlying mechanisms and aspects of pathophysiology of EoE to open up new avenues for effective diagnosis and treatments.

In recent years, our understanding of the pathophysiology of EoE has increased considerably, but the disease and underlying mechanisms remain complex and multifactorial. One of the key features of EoE is an impaired esophageal barrier, which allows food allergens to penetrate the esophageal mucosa. This can result in sensitization and a subsequent type 2 inflammatory response, which ultimately leads to further barrier impairment and disease progression.

In this project, we aim to unravel the complex cellular interactions that contribute to esophageal barrier dysfunction in EoE, as well as investigate the allergen-driven local immune responses occurring in the esophagus of patients. We will use in vitro and ex vivo studies to explore cellular interactions and immunomodulatory mediators and how these contribute to the local type 2 response. Furthermore, the effects of blocking IL-4/IL-13 signaling with monoclonal antibodies will be investigated in EoE patients and in in vitro experiments. These studies will provide further insight into the mechanisms underlying esophageal barrier pathology and type 2 inflammation in EoE, and have the potential to identify new targets for treatment.

Contact 
Marie Bek