Gastrointestinal tuft cells: Recent insights and next questions

Tuft cells are rare chemosensory epithelial cells distributed throughout mucosal barriers. Recent findings have established their roles in detecting helminths, protists, and bacteria and in regulating innate immunity and tissue physiology via secretion of effector molecules like IL-25, eicosanoids, and acetylcholine. This Review explores critical outstanding topics in gastrointestinal tuft cell biology, including what their evolved functions are beyond helminth sensing, how they detect different pathogens and dietary challenges, and why small intestinal tuft cells proliferate dramatically during type 2 responses. In addition, we explore how their differentiation is regulated by diverse epithelial-intrinsic and epithelial-extrinsic signals, whether they communicate with neurons in the intestine, and what roles they play in adaptive immunity. By organizing recent findings around these key topics, we highlight both progress and gaps in the understanding of how tuft cells integrate lumenal signals to regulate barrier immunophysiology.