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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Format: | Article |
Language: | English |
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The American Association of Immunologists
2021
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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. |
first_indexed | 2024-09-23T15:58:53Z |
format | Article |
id | mit-1721.1/136260 |
institution | Massachusetts Institute of Technology |
language | English |
last_indexed | 2024-09-23T15:58:53Z |
publishDate | 2021 |
publisher | The American Association of Immunologists |
record_format | dspace |
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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