Intestinal tuft cells: Sentinels, what else?

The intestinal epithelium plays crucial roles in maintaining gut homeostasis. A key function consists in constituting a physical and chemical barrier between self and non-self-compartments, and, based on its crosstalk with the luminal environment, in controlling activation of the host immune system. Tuft cells are a unique epithelial cell lineage, the function of which remained a mystery even 50 years after their initial discovery. The first function of intestinal tuft cells was recently described, with a central role in initiating type 2 immune responses following infection with helminth parasites. Since then, tuft cells have emerged as sentinel cells recognizing a variety of luminal cues, mediating the host-microorganisms crosstalk with additional pathogens, including viruses and bacteria. Although it can be anticipated that more functions will be discovered for tuft cells in the future, recent discoveries already propelled them at the forefront of gut mucosal homeostasis regulation, with important potential impact in gut physiopathology. This review focuses on intestinal tuft cells, from their initial description to the current understanding of their functions, and their potential impact in diseases.