Tuft Cells: Context- and Tissue-Specific Programming for a Conserved Cell Lineage

Tuft cells are found in tissues with distinct stem cell compartments, tissue architecture, and luminal exposures but converge on a shared transcriptional program, including expression of taste transduction signaling pathways. Here, we summarize seminal and recent findings on tuft cells, focusing on major categories of function-instigation of type 2 cytokine responses, orchestration of antimicrobial responses, and emerging roles in tissue repair-and describe tuft cell-derived molecules used to affect these functional programs. We review what is known about the development of tuft cells from epithelial progenitors under homeostatic conditions and during disease. Finally, we discuss evidence that immature, or nascent, tuft cells with potential for diverse functions are driven toward dominant effector programs by tissue- or perturbation-specific contextual cues, which may result in heterogeneous mature tuft cell phenotypes both within and between tissues.

Automated summary

Tuft cells are specialized cells found in tissues that have different stem cell compartments, tissue architecture, and luminal exposures. However, they share a common transcriptional program, including taste transduction signaling pathways. This article summarizes our current knowledge about tuft cells, focusing on their functions in initiating type 2 cytokine responses, coordinating antimicrobial responses, and their emerging roles in tissue repair. It also discusses how tuft cells develop from epithelial progenitors under normal conditions and during disease. Furthermore, it explores the evidence that immature tuft cells can differentiate into different functional programs depending on the contextual cues they receive, resulting in heterogeneity within and between tissues.