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Project

Food antigen-specific mast cell activation as a novel mechanism of abdominal pain

Irritable bowel syndrome (IBS) is a highly prevalent disorder of gastrointestinal (GI) tract characterized by altered bowel habit and abdominal visceral hypersensitivity (VHS). These IBS symptoms are usually triggered and exacerbate by dietary food, however, the underlying mechanisms remain to be identified. Mast cell activation, leading to activation and sensitization of afferent nerves, plays a crucial role in the development of VHS in IBS. We collected exciting evidence in patients and a recently developed mouse model of VHS that a local rather than a systemic response to food antigens to be involved in mast cell activation. In this project, I will investigate the hypothesis that, a local immune response possibly with local IgE antibodies targeted against food antigens may be involved in mast cell activation and VHS. I will further explore the role of local IgEs and evaluate to what extent local production of histamine releasing factor also contributes and may act synergistic with food antigen-specific IgE, both in our preclinical model and IBS patients. Finally, I aim to discover novel mechanisms, pathways and receptors potentially explaining the increased mast cell activation observed in IBS. The results of this project will be of crucial importance to improve our insight into the diagnosis and pathogenesis of IBS and will ultimately lead to more patient-specific treatment strategies for IBS.

Date:1 Oct 2018 →  30 Jun 2021
Keywords:food antigen-specific mast cell activation, abdominal pain
Disciplines:Endocrinology and metabolic diseases, Gastro-enterology and hepatology, Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences