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Immunohorizons. 2020 Jan 24;4(1):23-32. doi: 10.4049/immunohorizons.1900099.

The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis.

Howitt MR1,2,3, Cao YG4,2, Gologorsky MB3, Li JA3, Haber AL5, Biton M5,6, Lang J4,2, Michaud M4,2, Regev A5,7,8,9, Garrett WS1,2,5,10.

Author information

1
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115; mhowitt@stanford.edu wgarrett@hsph.harvard.edu.
2
Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115.
3
Department of Pathology, Stanford University, Stanford, CA 94305.
4
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115.
5
Broad Institute of MIT and Harvard, Cambridge, MA 02142.
6
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel.
7
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142.
8
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142.
9
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142; and.
10
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215.

Abstract

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 Tas1r3-deficient C57BL6/J mice both have severely impaired responses to tuft cell-inducing signals in the ileum, including the protozoa Tritrichomonas muris and succinate. In contrast, TAS1R3 is not required to mount an immune response to the helminth Heligmosomoides polygyrus, which infects the proximal small intestine. Examination of uninfected Tas1r3-/- 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.

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