The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis

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 understo...

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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
Other Authors: Howard Hughes Medical Institute
Format: Article
Language:English
Published: The American Association of Immunologists 2021
Online Access:https://hdl.handle.net/1721.1/136260
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author 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
author2 Howard Hughes Medical Institute
author_facet Howard Hughes Medical Institute
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
author_sort Howitt, Michael R
collection MIT
description 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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spelling mit-1721.1/1362602023-12-06T17:29:46Z The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis 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 Howard Hughes Medical Institute Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Biology 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. 2021-10-27T20:34:34Z 2021-10-27T20:34:34Z 2020 2021-07-22T17:33:44Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136260 en 10.4049/IMMUNOHORIZONS.1900099 ImmunoHorizons Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf The American Association of Immunologists ImmunoHorizons
spellingShingle 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
The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis
title The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis
title_full The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis
title_fullStr The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis
title_full_unstemmed The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis
title_short The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis
title_sort taste receptor tas1r3 regulates small intestinal tuft cell homeostasis
url https://hdl.handle.net/1721.1/136260
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