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Mas‐related gene receptor D is expressed in human gut and modulates sensory pathways during intestinal inflammation in mouse models

We have previously shown that the Mas‐related gene receptor D (MrgD) is expressed de novo in the mouse intestine during inflammation, specifically in intrinsic sensory neurons and mucosal mast cells (MMCs). We have also shown that MrgD deletion leads to increased MMC recruitment and sensory neuropeptide expression. These findings indicate role(s) for MrgD in the regulation of mastocytosis and (mast cell mediated)‐sensory neuromodulation. To further examine the effect of MrgD on intestinal function, we compared the motility of the ileum of healthy and Schistosoma mansoni‐infected wild‐type and MrgD−/− mice. Furthermore, to determine the mechanism of activation of MrgD in MMCs, calcium live cell imaging was performed on mouse bone marrow‐derived mast cells (BMMCs). MrgD deletion did not alter intestinal motility indicating that MrgD‐induced changes only influence the sensory pathways during inflammation. The MrgD ligand â‐alanine evoked a Ca2+ influx in a subset of BMMCs expressing MrgD, suggesting that â‐alanine can mediate MrgD activation during intestinal inflammation. As in mouse, MrgD was expressed in neurons and mast cells in the human intestine, suggesting translational potential. The findings justify the further exploration of MrgD as an experimental target in intestinal inflammatory pathologies, focussing on sensory perception and neuro‐immune interactions. Supported by FWO grant G.0179.08