Tuft cells, also know as brush border cells, are a rare and enigmatic epithelial cell type found in most endoderm-derived epithelia. Recent evidence is mounting that they play an important role during tissue homeostasis and in regulating the energy homeostasis along the gut brain axis. Ablation of tuft cells in the colonic mucosa impairs tissue regeneration after injury, while their depletion in intestinal adenomas results in marked regression of these lesions. Tuft cells are the only cell type in the gastrointestinal epithelium to secrete interleukin (IL)-25, an epithelial stress signal known to activate secretion of type 2 immune cytokines such as IL-13 in group 2 innate lymphoid cells (ILC2), an innate immune cell type resident predominantly at mucosal surfaces.
Importantly, our own data show a marked increase in tuft cells in early gastric tumours and depletion of tuft cells in these lesions results in significant reduction of tumour burden, accompanied by a drop in expression levels of IL-25 and IL-13 cytokines. Moreover, normal gastric organoids, grown ex vivo from glands lacking tuft cells, grow slower and this defect can be rescued by exogenous addition of IL-13. Importantly, in vivo administration of neutralizing anti-IL-25 antibody to gastric tumour bearing mice reduces overall tumour burden, phenocopying the results obtained after tuft cell depletion. These findings provide a compelling argument for a functional involvement of tuft cells and tissue-resident ILC2s in gastric tumourigenesis and suggest that this cross talk, primed to deal with parasitic infections, can be transformed into a tumour-promoting tuft cell/ILC2 axis