The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis

• Published in: ImmunoHorizons 2020-01, Vol.4 (1), p.23-32
• Main Authors: Howitt, Michael R, Cao, Y Grace, Gologorsky, Matthew B, Li, Jessica A, Haber, Adam L, Biton, Moshe, Lang, Jessica, Michaud, Monia, Regev, Aviv, Garrett, Wendy S
• Format: Article
• Language: English
• Subjects: Animals; Epithelial Cells - immunology; Epithelial Cells - metabolism; Gastrointestinal Microbiome; Homeostasis; Ileum - immunology; Ileum - parasitology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - parasitology; Intestine, Small - immunology; Intestine, Small - parasitology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nematospiroides dubius - immunology; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - immunology; Receptors, G-Protein-Coupled - metabolism; Strongylida Infections - immunology; Strongylida Infections - parasitology; Taste - physiology; Tritrichomonas - immunology
• ISSN: 2573-7732; 2573-7732
• DOI: 10.4049/immunohorizons.1900099

Tuft cells are an epithelial cell type critical for initiating type 2 immune responses to parasites and protozoa in the small intestine. To respond to these stimuli, intestinal tuft cells use taste chemosensory signaling pathways, but the role of taste receptors in type 2 immunity is poorly understood. In this study, we show that the taste receptor TAS1R3, which detects sweet and umami in the tongue, also regulates tuft cell responses in the distal small intestine. BALB/c mice, which have an inactive form of TAS1R3, as well as -deficient C57BL6/J mice both have severely impaired responses to tuft cell-inducing signals in the ileum, including the protozoa and succinate. In contrast, TAS1R3 is not required to mount an immune response to the helminth , which infects the proximal small intestine. Examination of uninfected mice revealed a modest reduction in the number of tuft cells in the proximal small intestine but a severe decrease in the distal small intestine at homeostasis. Together, these results suggest that TAS1R3 influences intestinal immunity by shaping the epithelial cell landscape at steady-state.