Multiple Roles and Therapeutic Targets of Tuft Cells in Inflammatory Bowel Disease

Tuft cells are rare epithelial chemosensory cells located in diverse organs, including the gut tract, and are characterized by large apical protrusions. Known as gut sentinels, tuft cells release widespread immunological effector molecules in response to gut luminal pathogens. Specifically, tuft cells are major regulators in initiating immune responses against certain nematodes and parasites. Another tuft cell property is the maintenance of gut hemostasis and modulation of the gut microbiome, which reduces intestinal inflammation. On the other hand, the pathophysiology of inflammatory bowel disease (IBD) is strongly linked to dysregulated immune responses, imbalances in the gut microbiome, and disruption of the mucosal barrier integrity. Hence, this review discusses tuft cell-mediated immune system response and its activation through luminal pathogens. It also addresses how the succinate-tuft cell axis plays a role in gut microbiome modulation. Finally, therapeutic options of tuft cell molecular effectors and their signaling pathways in IBD treatment are highlighted.