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Significance Tuft cells in the intestine are known to act as sentinels for infectious agents [e.g., helminths (worms) and bacterial microbiota] and express taste-signaling elements. In this work, the G protein-coupled receptor Sucnr1 was shown to be expressed specifically in tuft cells but not in other intestinal epithelial cells. Dietary succinate and perturbations in the microbiota activate tuft cells, and subsequently type 2 immunity, via tuft cell-expressed Sucnr1. Modulating this pathway using dietary succinate or specific Sucnr1 agonists may be a strategy for fighting bacterial and parasitic infections or other type 2 immune-related metabolic disorders such as obesity.

Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine