Expression and involvement of the Mas-related gene receptor MrgD in intestinal inflammation in the mouse

Abstract

Some members of the Mas-related gene receptor (Mrg) family have been suggested to play a role in mediating IgE-independent mast cell activation, as well as in neuroimmune communication. In a previous study, we observed an increased expression of some Mrgs, such as MrgD, in the murine ileum during intestinal inflammation. To further unravel the distribution and involvement of MrgD in intestinal inflammation, we compared the ileum of non-inflamed and Schistosoma mansoni-infected wild-type and MrgD–/– mice. In the wild-type mice, in the non-inflamed ileum, immunohistochemistry revealed no MrgD immunoreactivity (IR), whereas in the inflamed ileum, MrgD IR was observed in 5% of the myenteric neurons. Neurochemical coding revealed that the MrgD-expressing neurons were of the intrinsic primary afferent type. Moreover, MrgD IR was detected in mucosal mast cells (MMCs) in the inflamed ileum. In the MrgD–/– mice, no MrgD IR was detected, while an increased infiltration of MMCs was observed in the inflamed ileum. The expression of MrgD in sensory neurons and MMCs in the inflamed ileum of wild-types, and the increased MMC infiltration observed after MrgD deletion, suggest that MrgD is involved in nociceptive and mast cell responses during intestinal schistosomiasis. Future work should aim at elucidating the mechanisms underlying MrgD-mediated effects during intestinal inflammation.