2018 Volume 32 Issue 4 Pages 159-166
Mast cells are mainly located at the front line of surface barriers, such as the skin and gut mucosa. Mucosal mast cells are important for the clearance/elimination of parasites and pathogens via the release of chondroitin sulfate and proteases. These mediators are also involved in the pathogenesis of allergy and inflammatory symptoms. The main activator of mast cells, IgE, was discovered about 50 years ago; however, recent evidence has revealed the importance of IgE-independent activation pathways involved in the aggravation of allergy and inflammation. Based on past findings that mast cells are activated in the intestinal mucosa of patients with Crohn’s disease, we screened out the activator of mast cells in intestinal inflammation and found that extracellular adenosine tri-phosphate (ATP) was involved. Extracellular ATP is released from damaged cells, but some species of commensal bacteria also actively release ATP into the extracellular space, and require it for “commensal mutualism”. Intriguingly, the response to extracellular ATP was limited in skin mast cells. This phenotype was considered to be a tissue-specific regulation of mast cell function, which was mediated by mesenchymal cells. The disruption of skin-specific regulation of mast cells causes chronic inflammation in the skin and depends on skin commensal bacterial stimulation. Taken together, the maintenance of surface barriers in the body is tightly regulated by immune-mesenchymal interactions. It is expected that the development of novel therapeutic approaches for chronic inflammation, which can be considered as a disruption of “symbiosis and elimination” mechanisms, will be used to target errors of tissue-specific immune (e.g. mast cells) responses and mesenchymal cell interactions.
