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Functional characterization of human mast cells and basophils in the pathophysiology of diarrhea-predominant irritable bowel syndrome.

Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders, affecting around 11% of the population. The underlying cause of IBS is still largely unknown. Recently the importance of the immune system and more specifically mast cells (MC) and basophils (BP) was highlighted. These immune cells are heavily influenced by their surroundings and release mediators affecting gut sensitivity in response. In this research project we would like to elucidate the involvement of both mast cells and basophils in the development of IBS, using novel but validated immunological methods, and to study the mediators involved in mast cell and basophil activation in IBS, focusing on the diarrhea-predominant subtype. We will further subdivide these patients according to the underlying cause, concentrating on postinfectious onset and central risk factors (depression and anxiety). First of all, we will study whether BP and cultured MC of IBS patients are immunologically different compared to healthy controls. Subsequently we will study cultured MC in the presence of a large intestinal biopsy extract of IBS patients and healthy controls, to determine whether the gut environment influences MC reactivity. Lastly, we will look at the role of mas-related G protein-coupled receptors (MRGPR), a class of receptors involved in MC activity and in processing of gut pain, as potential therapeutic targets in IBS.
Date:1 Oct 2018 →  30 Sep 2020
Disciplines:Gastro-enterology and hepatology