Tuft cell integration of luminal states and interaction modules in tissues

Abstract

Chemosensory processes are integral to the physiology of most organisms. This function is typically performed by specialized cells that are able to detect input signals and to convert them to an output dedicated to a particular group of target cells. Tuft cells are cholinergic chemosensory epithelial cells capable of producing immunologically relevant effector molecules. They are scattered throughout endoderm-derived hollow organs and function as sensors of luminal stimuli, which has been best studied in mucosal barrier epithelia. Given their epithelial origin and broad distribution, and based on their interplay with immune pathways, tuft cells can be considered a prototypical example of how complex multicellular organisms engage innate immune mechanisms to modulate and optimize organ physiology. In this review, I provide a concise overview of tuft cells and discuss how these cells influence organ adaptation to dynamic luminal conditions.

Keywords: Aversive responses; Chemosensation; Tuft cells; Type 2 immunity.

Fig. 1

Summary of tuft cell interaction modules. Stimulation of tuft cells with luminal agonists triggers the release of one or multiple tuft cell effector molecules in a process that remains incompletely characterized. Known effector molecules include acetylcholine (various tissues), ATP (type II taste cells), IL-25 (small intestine), cysteinyl leukotrienes (CysLTs) (small intestine, airways), and prostaglandin D₂ (PGD₂) (small intestine, pancreas). Acetylcholine has a relatively broad action profile and is primarily associated with acute aversive responses in multiple organs via effects on ciliated cells and afferent nerve fibers (see text). ATP functions as a critical second messenger for the signaling of gustatory information from type II taste cells to afferent fibers in the oral taste buds [30]. IL-25 and CysLTs cooperatively stimulate the production of IL-13 and other type 2 cytokines in group 2 innate lymphoid cells (ILC2s) of the small intestine lamina propria (see text). Recent studies revealed roles of PGD₂ in injury-associated pancreatic tumorigenesis [31] and small intestinal type 2 responses [32] through effects on incompletely defined immune and epithelial cell populations. IL-25 and tuft cell-derived eicosanoids appear to be predominantly involved in the regulation of epithelial remodeling