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Project

Role of eosinophils in gut inflammation and fibrosis in inflammatory bowel disease

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory intestinal diseases characterized by a relapse-remitting disease course and commonly affecting young individuals. Due to an excessive accumulation of extracellular matrix (ECM), caused by inflammation and healing, fibrostenosis can occur. Fibrostenosing IBD, most commonly seen in CD patients, is the major cause of complications such as stricture formation, intestinal obstruction and the need for resection. Previously, IBD studies have mainly focused on modifications in the adaptive immune responses. However, this study will primarily focus on alterations in the innate immune system. Prior research has revealed an accumulation of neutrophils and eosinophils in the colon, indicating myeloid derived cells could be key players in the induction of chronic inflammation and fibrogenesis in IBD. This project therefore aims to identify the role of eosinophils in chronic intestinal inflammation and fibrosis. In order to achieve the aim, eosinophils will be depleted in several murine models. In order to subsequently translate these findings to a human setting, we have an ongoing collaboration with the Leuven IBD lab and the Pathology Department of UZ Leuven. The composition of several innate immune cells, both in peripheral blood and colon tissue, will be studied in patients with IBD to potentially identify a non-invasive biomarker for disease activity. Furthermore, on resection specimen of fibrostenotic IBD patients, the composition of the different layers (mucosa vs. submucosa) of fibrotic tissue will be studied to pinpoint the real contributor of fibrosis. Lastly, we aim to assess the effect of current therapies on the immune cell landscape, with a specific interest in the eosinophils.

Date:5 Mar 2020 →  5 Mar 2024
Keywords:Inflammatory Bowel Disease (IBD), Crohn's Disease (CD), Ulcerative Colitis (UC), Fibrostenotic disease, Innate immunity
Disciplines:Gastro-enterology, Inflammation, Innate immunity
Project type:PhD project