Tuft Cells

Tuft cells, also known as brush cells, have been identified widely in the gastrointestinal tract (stomach, large and small intestine), and within salivary glands, bile ducts, and respiratory tract. Tuft cells were named for their unique morphology, characterized by a thick tuft of long microvilli projecting into the lumen from their apical face. They seem to be related to taste cells, which which they share sensory molecules involved in the transduction of bitter and umami tastes.

The major role of tuft cells is to initiate T helper, type 2 (Th2) immune responses to parasites, including both intestinal helminths and protozoa. This function was recognized by finding large numbers of tuft cells in the intestinal epithelium of parasitized mice and a clear reduction in tuft cell numbers when mice were treated to eliminate those parasites. Elevation of tuft cell numbers is also observed in other cases of gastrointestinal pathology. In essense, tuft cells act as sentinals to alert the inate immune system of the presence of parasites, initiating a potent immune response against them.

How are tuft cell numbers regulated and signaling to immune cells accomplished? The presence of parasites in the intestinal lumen is sensed by tuft cells, which respond by secreting the cytokine interleukin 25 into the underlying tissue, where it stimulates innate lymphoid cells to secrete another cytokine - interleukin 13. Interleukin 13 binds to receptors on crypt stem cells, promoting differentiation of their progeny into additional tuft cells. This positive feedback cycle thereby explains how parasitic infestation in the intestine results in increased numbers of tuft cells. When parasites are removed, the interleukin 25 signal dissipates, interleukin 13 secretion goes down, and the stem cells are no longer stimulated to make additional tuft cells.

References and Reviews

• Gerbel F, Jay P. Intestinal tuft cells: epithelial sentinels linking luminal cues to the immune system. Mucosal Immunol 2016; 9: 1353-59.
• Howitt MR, Lavoie S, Michaud M, etc. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 2016; 351: 1329–1333.
• Kaji I, Kaunitz JD. Luminal chemosensing in the gastroduodenal mucosa. Curr Opin Gastroenterol 2017; 33: 439–445.

Updated December 2018. Send comments to Richard.Bowen@colostate.edu