Abstract
Mast cells are immune cells that are typically associated with allergic reactions at mucosal surfaces. Here, mast cells form operating units with sensory nerves and can contribute to sensations of itch and pain. In the context of Irritable Bowel Syndrome (IBS), a frequently occurring gastrointestinal disorder characterized by abnormal pain signaling (i.e. visceral hypersensitivity), the involvement of abnormal mast cell functioning has been recognized, but the exact receptors and signaling mechanisms driving this aberrant mast cell functioning remain poorly understood. In this respect, the presence of a novel IgE-independent, 'pseudo-allergic' pathway of mast cell activation pathway in the colon, consisting of mouse Mrgprb2 and its human counterpart MRGPRX2, was recently discovered our lab. In this PhD project, I will focus on the specific role of this novel Mrgprb2/X2-mediated signaling pathway as a driver of aberrant mast cell functioning in the pathophysiology of IBS and associated visceral hypersensitivity. In this way, my PhD project might generate a novel paradigm in our understanding of IBS pathophysiology and may form a solid foundation for further studies into the therapeutic potential of this pathway in these conditions.
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