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Review
. 2024 Feb 12:86:479-504.
doi: 10.1146/annurev-physiol-042022-030310. Epub 2023 Oct 20.

Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health

Jennifer B Silverman  1 , Paige N Vega  1 , Matthew J Tyska  1 , Ken S Lau  1
Affiliations
Review

Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health

Jennifer B Silverman et al. Annu Rev Physiol. .

Abstract

Tuft cells are a rare and morphologically distinct chemosensory cell type found throughout many organs, including the gastrointestinal tract. These cells were identified by their unique morphologies distinguished by large apical protrusions. Ultrastructural data have begun to describe the molecular underpinnings of their cytoskeletal features, and tuft cell-enriched cytoskeletal proteins have been identified, although the connection of tuft cell morphology to tuft cell functionality has not yet been established. Furthermore, tuft cells display variations in function and identity between and within tissues, leading to the delineation of distinct tuft cell populations. As a chemosensory cell type, they display receptors that are responsive to ligands specific for their environment. While many studies have demonstrated the tuft cell response to protists and helminths in the intestine, recent research has highlighted other roles of tuft cells as well as implicated tuft cells in other disease processes including inflammation, cancer, and viral infections. Here, we review the literature on the cytoskeletal structure of tuft cells. Additionally, we focus on new research discussing tuft cell lineage, ligand-receptor interactions, tuft cell tropism, and the role of tuft cells in intestinal disease. Finally, we discuss the implication of tuft cell-targeted therapies in human health and how the morphology of tuft cells may contribute to their functionality.

Keywords: chemosensation; cytoskeleton; differentiation; inflammation; microbiome; tuft cells.

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Figures

Figure 1
Figure 1
Tuft cell cytoskeletal morphology. (a) Graphic depicting major organelles and cytoskeletal components and their spatial organization within a tuft cell. Panel adapted from images created with BioRender.com. (b, top) En face scanning electron microscopy image demonstrating tuft cell apical protrusions next to neighboring microvilli. (Bottom) En face transmission electron microscopy image of tuft cell apical protrusions next to neighboring microvilli. (c, top) Lateral transmission electron microscopy image of tuft cell; yellow arrows point to core actin bundles. (Bottom) Phalloidin stain for F-actin.
Figure 2
Figure 2
(a) Illustration depicting signal code for epithelial cell differentiation and specification of tuft-1 and tuft-2 cells. (b) Graphic depicting the current knowledge of organ-/tissue-specific tuft cell ligands and their corresponding receptors. Tuft cell effectors that are downstream of many of these ligand-receptor interactions are listed below. Abbreviations: ACh, acetylcholine; CysLT, cysteinyl leukotriene; DRD3, dopamine receptor D3; EGF, epidermal growth factor; FFAR2, free fatty acid receptor 2; FFAR3, free fatty acid receptor 3; GPR64/ADGRG2, adhesion G protein–coupled receptor G2; IL-25, interleukin 25; PGD2, prostaglandin D2; P2Y2, P2Y purinoceptor 2; POU2F3, POU class 2 homeobox 3; SIRT6, sirtuin 6; SOX4, SRY (sex determining region Y) box 4; SPIB, Spi-B (transcription factor); STAT6, signal transducer and activator of transcription 6; SUCNR1, succinate receptor 1; TAS1R, taste 1 receptor; TAS1R3, taste 1 receptor member 3; TAS2R, taste 2 receptor; TAS2R117, taste 2 receptor member 117; TAS2R136, taste 2 receptor member 136; TAS2R143, taste 2 receptor member 143; TAS3R, taste 3 receptor; VMN2R26, vomeronasal type-2 receptor 26; WNT, wingless/integrated, NOTCH, neurogenic locus notch homolog protein.
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