The taste receptor TAS1R3 regulates small intestinal tuft cell homeostasis
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PROVIDER: PRJNA589590 | ENA |
REPOSITORIES: ENA
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Project description:Tuft cells are an epithelial cell subset 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. Here, 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.
2020-01-09 | GSE140395 | GEO
Project 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.
| S-EPMC7197368 | biostudies-literature
Project description:Intestinal homeostasis is dynamically coordinated by various types of epithelial cells fulfilling their specific functions. Tuft cells as chemosensory cells have emerged as key players of the host response, such as innate immunity. Tuft cells are also critical for the restoration of intestinal architecture upon damage, thereby contributing to inflammatory bowel diseases (IBDs) characterized by defective intestinal barrier integrity. However, the molecular mechanism of how tuft cell homeostasis is controlled remains obscure. Recent studies have identified single-nucleotide polymorphisms in the inositol polyphosphate multikinase (IPMK) gene associated with IBD predisposition. IPMK, an essential enzyme for inositol phosphate metabolism, has been known to mediate major biological events such as growth. To investigate the functional significance of IPMK in gut epithelium, we generated intestinal epithelial cell (IEC)-specific Ipmk knockout (IPMKΔIEC) mice. Whereas IPMKΔIEC mice developed normally and showed no intestinal abnormalities during homeostasis, Ipmk deletion aggravated dextran sulfate sodium (DSS)-induced colitis, with higher clinical colitis scores, and elevated epithelial barrier permeability. Surprisingly, no apparent defects in epithelial growth signaling pathway and inflammation were found in DSS-challenged, IPMK-deficient colons. Rather, Ipmk deletion led to a significant decrease in the number of tuft cells without influencing other intestinal epithelial cells. Ipmk deletion in the gut epithelium was found to reduce choline acetyltransferase but not cytokines (e.g., IL-25), suggesting selective loss of cholinergic signaling. Single-cell RNA-sequencing of mouse colonic tuft cells (EpCAM+/Siglec F+) and immunohistochemistry revealed three populations of tuft cells and further showed that, in IPMKΔIEC mice, a transcriptionally inactive tuft club cell population was markedly expanded, and neuronal-related tuft cells were relatively decreased, supporting the abnormal development of tuft cells without IPMK functions. Thus, IPMK acts as a physiological determinant of colonic tuft cell homeostasis, thereby mediating tissue regeneration upon injury.
2022-10-26 | GSE200284 | GEO
Project description:Tuft cells as a type of intestinal epithelial cells exist in epithelial barriers that play a critical role in immunity against parasite infection. It remains elusive about whether Tuft cells participate in bacterial eradication. Here we identify Sh2d6 as a signature marker for CD45+ Tuft-2 cells. Tuft-2 cells are derived from Lgr5+ intestinal stem cells but not bone marrow cells. Depletion of Tuft-2 cells is susceptible to bacterial infection. Tuft-2 cells quickly expand over bacterial infection and sense bacterial metabolite N-undecanoylglycine through vomeronasal receptor Vmn2r26. Mechanistically, Vmn2r26 engagement with N-undecanoylglycine activates GPCR-PLCγ2-Ca2+ signal axis, which initiates prostaglandin D2 (PGD2) production. PGD2 enhances mucus secretion of Goblet cells and induces antibacterial immunity. Moreover, Vmn2r26 signaling also promotes SpiB expression, which is responsible for Tuft-2 cell development and expansion over bacterial challenge. Our findings reveal a novel function of Tuft-2 cells in immunity against bacterial infection through Vmn2r26-mediated recognition of bacterial metabolites. We used microarrays to detail the gene expression of Tuft-2 cells compared with non Tuft-2 epithelial cells under Shigella infection.
2021-09-24 | GSE184675 | GEO
Project description:We previously identified Dclk1, a tuft cell marker, marks tumor stem cells (TSCs) in mouse intestinal tumors. In this study, we have identified IL17RB as a cell surface marker distinctively expressed by Dclk1+ tuft-like tumor cells in mouse intestinal tumors. Using this tuft cell marker, we compared and analyzed the transcriptome of Lgr5-tuft marker-, Lgr5+tuft marker-, Lgr5-tuft marker+, and Lgr5+tuft marker+ tumor cells. These analyses revealed that tuft-like tumor cells in the intestinal tumors comprise two distinct subsets: highly differentiated tuft-like tumor cells (Lgr5-tuft marker+ cells) and tuft-like tumor cells with TCS potential (Lgr5+tuft marker+ cells).
2021-02-19 | GSE118853 | GEO
Project description:Taste stem/progenitor cells from the mouse posterior tongue have been recently used to generate taste bud organoids. However, the inaccessible location of the taste receptor cells is observed in conventional organoids. Here, we established a suspension culture method for fine tuning of taste bud organoid by apicobasal polarity alteration to form the accessible localization of taste receptor cells in organoid. Compared to conventional Matrigel-embedded organoids, suspension-cultured organoids showed comparable differentiation and renewal rates to those of taste buds in vivo and exhibited functional taste receptor cells and cycling progenitor cells. Accessible taste receptor cells on the outer region of taste bud organoids enabled the direct application of calcium imaging for evaluating the taste response. Moreover, suspension-cultured organoids could be genetically altered using gene editing methods. Suspension-cultured taste bud organoid harmoniously integrated with the recipient lingual epithelium; maintained the taste receptor cells and gustatory innervation capacity. Thus, we propose that suspension-cultured organoids may provide efficient model for taste research including taste bud development, regeneration and transplantation
2021-12-25 | GSE191169 | GEO
Project description:The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To clarify how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (Just EGFP Death Inducing) CD8+ T cells into tuft cell reporter mice (Gfi1b-GFP). Surprisingly, some tuft cells partially resist JEDI CD8+ T cell-mediated killing – unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells – despite seemingly normal antigen presentation. When targeting tuft cells, JEDI CD8+ T cells predominantly adopt a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. Importantly, JEDI CD8+ T cells neither clear nor prevent MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen (e.g., GFP).
2023-12-08 | GSE249744 | GEO
Project description:The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To clarify how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (Just EGFP Death Inducing) CD8+ T cells into tuft cell reporter mice (Gfi1b-GFP). Surprisingly, some tuft cells partially resist JEDI CD8+ T cell-mediated killing – unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells – despite seemingly normal antigen presentation. When targeting tuft cells, JEDI CD8+ T cells predominantly adopt a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. Importantly, JEDI CD8+ T cells neither clear nor prevent MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen (e.g., GFP).
2023-12-08 | GSE242118 | GEO
Project description:The goal of the study was to sequence mRNA from tuft cells (identified as CD45-;EpCAM+;IL-25+ using Flare25 reporter mice) in the epithelia of thymus and small intestine. As a control, non-tuft epithelial cells (CD45-;EpCAM+;IL-25-) were also isolated. The data were used to compare tuft cell markers between the small intestine and thymus.
2018-05-19 | GSE114668 | GEO
Project description:Taste buds on the tongue are collections of taste receptor cells (TRCs) that detect sweet, sour, salty, umami and bitter stimuli. Like non-taste lingual epithelium, TRCs are renewed from basal keratinocytes, many of which express the transcription factor SOX2. Genetic lineage tracing has shown SOX2+ lingual progenitors give rise to both taste and non-taste lingual epithelium in the posterior circumvallate taste papilla (CVP) of mice. However, SOX2 is variably expressed among CVP cells suggesting that their progenitor potential may vary. Using transcriptome analysis and organoid technology, we show highly expressing SOX2+ cells are taste-competent progenitors that give rise to organoids comprising both TRCs and lingual epithelium, while organoids derived from low-expressing SOX2+ progenitors are composed entirely of non-taste cells. Hedgehog and WNT/ß-catenin are required for taste homeostasis in adult mice, but only WNT/ß-catenin promotes TRC differentiation in vitro and does so only in organoids derived from higher SOX2+ taste lineage-competent progenitors.
2023-02-07 | GSE207624 | GEO