The Role of Mast Cells in Irritable Bowel Syndrome

Abstract

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but its treatment is unsatisfactory as its pathophysiology is multifactorial. The putative factors of IBS pathophysiology are visceral hypersensitivity and intestinal dysmotility, also including psychological factors, dysregulated gut-brain axis, intestinal microbiota alterations, impaired intestinal permeability, and mucosal immune alterations. Recently, mucosal immune alterations have received much attention with the role of mast cells in IBS. Mast cells are abundant in the intestines and function as intestinal gatekeepers at the interface between the luminal environment in the intestine and the internal milieu under the intestinal epithelium. As a gatekeeper at the interface, mast cells communicate with the adjacent cells such as epithelial, neuronal, and other immune cells throughout the mediators released when they themselves are activated. Many studies have suggested that mast cells play a role in the pathophysiology of IBS. This review will focus on studies of the role of mast cell in IBS and the limitations of studies and will also consider future directions.

Figure 1

The putative role of mast cells in IBS. Both symptoms of IBS, abdominal pain and stool changes, could be mediated by intestinal mast cells. Located close to the intrinsic or extrinsic nerve fibers, mast cells can stimulate the adjacent nerve fibers conveying nociceptive signals to the CNS. These signals could be perceived as painful by interaction with other contributing factors including cognitive and affective function by cerebral cortical and subcortical regions. Mast cells activated by serotonin secreted from enteroendocrine cells release mediators and then the mediators evoke local physiologic reflex response by intrinsic and extrinsic nervous systems, altering peristalsis, perfusion, and secretion which impact intestinal transit and luminal fluid content, therefore developing diarrhea or constipation as well as abdominal pain. Also, mast cells activated by serotonin or by stress-induced efferent neuronal stimulation degranulate mediators, which in this time activate other immune cells. These immune cells may be involved in epithelial secretion or mucosal permeability changes. This intestinal barrier dysfunction may be led by mast cell-associated degradation of various epithelial gap junctional proteins.