Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance

ABSTRACT: Epithelial cells secrete chloride to regulate water release at mucosal barriers, supporting both homeostatic hydration and the “weep” response that is critical for Type 2 immune defense against parasitic worms (helminths). Epithelial tuft cells in the small intestine sense helminths and release cytokines and lipids to activate Type 2 immune cells, but whether they regulate epithelial secretion is unknown. Here we found that tuft cell activation rapidly induced epithelial chloride secretion in the small intestine. This response required tuft cell sensory functions and tuft-cell-derived acetylcholine (ACh), which acted directly on neighboring epithelial cells to stimulate chloride secretion, independent of neurons. Maximal tuft cell-induced chloride secretion coincided with immune restriction of helminths, and clearance was delayed in mice lacking tuft cell-derived ACh, despite normal Type 2 inflammation. Thus, we have uncovered an epithelium-intrinsic response unit that uses ACh to couple tuft cell sensing to the secretory defenses of neighboring epithelial cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE262198 | GEO | 2024/05/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance

Project description:Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance

| PRJNA1090606 | ENA

Loss of Elp3 impairs the immune response to helminths by blocking intestinal tuft cell differentiation

Project description:Intestinal tuft cells are critical in anti-helminth immunity by producing IL-25, which triggers IL-13 secretion by activated group 2 innate lymphoid cells (ILC2s) in order to ultimately expand both goblet and tuft cells. Translational reprogramming is involved in intestinal tuft cell differentiation but the role of tRNA modifications in this process is unknown. We show here that epithelial Elp3, a tRNA-modifying enzyme, promotes tuft cell differentiation and is consequently critical for IL-25 production, ILC2 activation, goblet cell expansion and control of N. brasiliensis infection in mice. Elp3 is essential for the IL-13-dependent induction of some glycolytic enzymes such as Hexokinase 1 and Aldolase A and consequently links specific metabolic pathways to tuft cell differentiation. Importantly, loss of epithelial Elp3 in the intestine blocks the translation of Nprl2, a mTORC1 inhibitor, which consequently enhances mTORC1 activation and stabilizes Atf4 in both transit amplifying and progenitor cells. Likewise, Atf4 overexpression in mouse intestinal epithelium blocks tuft cell differentiation and impairs the control of intestinal helminth infection. Collectively, our data define Atf4 as a negative regulator of tuft cell differentiation and provide insights into mechanisms through which some tRNA modifications promote a type 2 immune response to parasites in the intestine.

2024-07-25 | GSE241625 | GEO

Intestinal and thymic tuft cell RNA-seq

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

The taste receptor TAS1R3 regulates small intestinal tuft cell homeostasis

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

Tissue specific gene expression of epithelial tuft cells from small intestine and gallbladder in mouse

Project description:Rare chemosensory epithelial cells called tuft cells have known roles in small intestinal regulation of type 2 cytokine producing Group 2 innate lymphoid cells. To understand the phenotype of tuft cells in another tissue, the extrahepatic biliary tree, we performed RNAseq analysis on tuft cells and non-tuft epithelial cells from small intestine and gallbladder of the mouse.

2022-03-01 | GSE194035 | GEO

Tissue tuft cell mRNA sequencing

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 5 different murine tissues: trachea, thymus, colon, gall baldder, small intestine. As a control, non-tuft epithelial cells (CD45-;EpCAM+;IL-25-) were also isolated. The data were used to identify differentially expressed genes across tuft cells from different tissues and to define a transcriptional tuft cell "signature" that is common to all tissues analyzed but absent in the non-tuft epithelial cells.

2018-05-05 | GSE114067 | GEO

Gene expression from tuft cells under scopolamine treatment

Project description:In our study, we investigated the effect of muscarinic receptor blockade on murine intestinal stem cell activity and differentiation. Following pharmacologic (scopolamine) and genetic muscarinic receptor interruption (M3R-KO, M1R-KO; Vil-Cre x M3R fl/fl, Vil-Cre x M1R fl/fl mice, respectively), we observe a selective, significant expansion of DCLK1-positive tuft cells. This is primarily sensed by endocrine Prox1-positive cells (Prox1-CreERT2 x M3R fl/fl mice), while Lgr5-positive ISCs respond with a reduction of their cellular activity (Lgr5-EGFP-IRES-CreERT2 x M3R fl/fl mice). To characterize expanding tuft cells in more detail, adult BAC transgenic DCLK1-DTR-ZSgreen reporter mice generated in our lab were treated with scopolamine or sodium chloride as controls (Sham) for 7d and live jejunal EPC-positive/ZSgreen-positive cells sorted. Extracted total RNA from sorted ZSgreen-positive cells of scopolamine- and sham-treated mice was sequenced. Further analysis revealed that expanding tuft cells orchestrate an increase in mucosal acetylcholine, which maintained intracellular signaling pathways such as p-ERK/ERK 1/2 or TCF-1/7. Finally, acute irradiation injury was employed to investigate the importance of this regulatory circuit for tissue homeostasis. Indeed, tissue injury in Vil-Cre x M3R fl/fl mice resulted in a severe reduction of epithelial DCLK1-positive tuft cells, concomitant to reduced mucosal Ach levels as well as intracellular PI3K-/p-ERK levels. Therefore, DCLK1-positive tuft cells appear essential for the maintenance of a regular intestinal cholinergic niche.

2019-11-01 | GSE138365 | GEO

Genetic mapping reveals Pou2af2-dependent tuning of tuft cell differentiation and intestinal type 2 immunity

Project description:Chemosensory epithelial tuft cells contribute to innate immunity at barrier surfaces, but their differentiation from epithelial progenitors is not well understood. Here we exploited differences between inbred mouse strains to identify an epithelium-intrinsic mechanism that regulates tuft cell differentiation and tunes innate type 2 immunity in the small intestine. Balb/cJ (Balb) mice had fewer intestinal tuft cells than C57BL/6J (B6) mice and failed to respond to the tuft cell ligand succinate. A majority of this differential succinate response was determined by a single genetic locus from 50-67Mb on chromosome 9 (Chr9). Congenic Balb mice carrying the B6 Chr9 locus had elevated baseline numbers of tuft cells and responded to succinate. The Chr9 locus includes Pou2af2, a transcriptional cofactor essential for tuft cell development. Epithelial crypts expressed a previously unannotated short isoform of Pou2af2 that uses a novel transcriptional start site and encodes a non-functional protein. Low tuft cell numbers and the resulting lack of succinate response in Balb mice was explained by a preferential expression of the short isoform. Physiologically, differential Pou2af2 isoform usage tuned innate type 2 immunity in the small intestine. Balb mice maintained responsiveness to helminth pathogens while ignoring commensal Tritrichomonas protists and reducing norovirus burdens.

2022-11-04 | GSE217040 | GEO

Tuft cells act as regenerative stem cells in the human intestine

Project description:In mice, intestinal tuft cells have been described as a long-lived, post-mitotic cell type of which two distinct subsets have been identified, named tuft-1 and tuft-2.By combining analysis of primary human intestinal resection material with organoid technology, we identify four distinct states of human tuft cells, two of which overlap with their murine counterparts. We show that tuft cell development depends on the presence of Wnt ligands, and that its numbers rapidly increase upon interleukin (IL)-4 and IL-13 exposure, as reported previously in mouse. This, however, is induced through proliferation of pre-existing tuft cells, rather than through increasedde novo generation from stem cells. Indeed, proliferative tuft cells occurin vivoboth in adult and in fetal human intestine. Single mature proliferating Tuft cells can form organoids that contain all intestinal epithelial cell types. Unlike stem- and progenitor cells, human tuft cells survive irradiation damage and retain the ability to generate all other epithelial cell types. Accordingly, organoids engineered to lack tuft cells fail to recover from radiation-induced damage. Thus, tuft cells represent a damage-induced reserve intestinal stem cell pool in humans.

2024-05-01 | GSE233451 | GEO

Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine by vomeronasal receptor Vmn2r26

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data