Ileum/colon treated with succinate
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ABSTRACT:
PROVIDER: PRJNA608465 | ENA |
REPOSITORIES: ENA
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Project description:An inverse correlation between countries endemic for helminth infestation and Crohn's disease (CD) incidences has been reinforced by anecdotal but successful cases of helminth therapy for CD. Recent studies have revealed that tuft cells in the small intestine are critical for sensing helminths and directing a type 2 immune response to counteract colonization. Here, we establish an inverse relationship between chemosensory tuft cells and local tissue inflammation in CD patients as well as an established mouse model of TNF-á-induced Crohn's-like ileitis (TNFÄARE). Using a combination of mouse and organoid models, single-cell RNA-sequencing, multiplex immunofluorescence, computational analysis, metabolite mass spectrometry, and microbiome sequencing and manipulation, we identified Atonal Homolog 1 (ATOH1)-independent tuft cells, as opposed to ATOH1-dependent tuft cells, to be responsive to the commensal microbiome through the tricarboxylic acid (TCA) cycle metabolite succinate. To evaluate the ability of the malleable, ATOH1-independent tuft cell population to suppress intestinal inflammation, we administered succinate to TNFÄARE animals post onset of ileal inflammatory disease. We observed significantly reduced pathology that is exquisitely dependent on succinate-induced tuft cell specification in the disease model, leading to an anti-helminth response previously shown to suppress inflammation. Inflammation suppression was triggered by cytokines critical to anti-helminthic response, such as IL-22, IL-25, and IL-13. We provide evidence implicating the modulatory role of intestinal tuft cells in chronic intestinal inflammation, which could enable the development of CD therapies around leveraging this rare and elusive cell type.
2020-08-24 | GSE145829 | GEO
Project description:This study is a comparative proteomics study of FACS sorted Muc2 expressing and non expressing cells in mouse ileum and colon.
2021-04-19 | PXD011527 | Pride
Project description:Ileum and colon mucosa Raw sequence reads
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Project description:The gene expression of ileum, jejunum and colon.
2020-12-21 | GSE143342 | GEO
Project description:Succinate administration induced characteristic type 2 immunity via the tuft cell-ILC2 immune circuit, significantly ameliorating DSS-induced colonic inflammation by enhancing bactericidal capacity, reducing intestinal permeability, and modulating cytokine profiles in the colon. Succinate promoted expansion of myeloid cells in peripheral blood, mesenteric lymph nodes (MLN), and colonic lamina propria. The protective effect of succinate was abolished in Ccr2-/- mice but maintained in Rag1-/- mice. Adoptive transfer of monocytes from succinate-treated donors to naïve recipient mice mitigated intestinal inflammation. RNA-seq revealed increased expression of proinflammatory cytokines IL-1β, IL-6, and lactate upon lipopolysaccharide (LPS) stimulation in monocytes from succinate-treated mice. Moreover, the critical role of the IL-4Rα/Hif-1α axis in succinate-mediated protection was delineated.
2024-02-28 | GSE255272 | GEO
Project description:Gene expression profile of ileum, jejunum and colon
| PRJNA600172 | ENA
Project description:Proximal Colon (i.e. proximal to hepatic flexure) versus Terminal ileum Transcriptomes (Affymetrix array U133A). All subjects were operated on for proximal-colon tumor (biopsies of proximal-colon normal mucosa were made at more than 5 cm from the site of the tumor).
2021-03-03 | E-MTAB-10164 | biostudies-arrayexpress
Project description:The occurrence of many neonatal inflammatory intestinal diseases in preterm infants highlights the susceptibility of the immature intestine to respond inadequately to nutrient and microbes. A better understanding of the functional intestinal development is essential for the design of optimal treatments ensuring survival and growth of premature infants. The purpose of this study was to evaluate the gene expression profiles of the developing human ileum and colon at mid-gestation. Our results showed that more than 11% of the genes were differentially expressed between ileum and colon. Pathway analysis revealed an even higher level of transcriptional dissimilarity between the developing ileum and the colon including 35% of the significant cellular, molecular and physiological functions and 85% of the canonical pathways. Segment-specific/over-expressed functions in the ileum included a number of amino acid, vitamin and mineral metabolisms and lymphoid tissue structure and development reflecting the high level of maturity of the small intestine as compared to the colon in which cell cycle, cell morphology and actin cytoskeleton, integrin and ERK/MAPK signaling were the predominant functions. All together, functional clustering analysis of the differentially expressed genes revealed important functional difference between the two segments namely to an unexpected relative immaturity of the colon.
2011-01-01 | GSE20983 | GEO
Project description:Hypothesis: Gene expression differences in biopsies from patients with inflammatory bowel disease can be used to identify molecular heterogeneity within patients with active disease. Methods: Patients with a diagnosis of Crohn's disease, ulcerative colitis or normal healthy controls (with or without infectious colitis) underwent ileocolonoscopy. In healthy controls, biopsies were taken in the sigmoid colon (n=21), ascending/descending colon (n=25) and the terminal ileum (n=12). In patients with Crohn's disease, biopsies were taken in the ascending/descending colon (n=107) and terminal ileum (n=70) in uninflamed areas in all patients; in patients with mucosal lesions, additional biopsies were taken in inflamed regions of the ascending/descending colon (n=35) and terminal ileum (n=55). In ulcerative colitis patients, paired uninflamed sigmoid (n=48) and inflamed sigmoid biopsies (n=46) were taken. Biopsies were placed in RNAlater at the clinical site, frozen and shipped to Genentech, where they were disrupted using TissueLyzer beads, then RNA was isolated using RNeasy columns. RNA was hybridized to Agilent human 4x44kv1 arrays, dual channel, using universal reference.
2021-07-26 | GSE179285 | GEO
Project description:The occurrence of many neonatal inflammatory intestinal diseases in preterm infants highlights the susceptibility of the immature intestine to respond inadequately to nutrient and microbes. A better understanding of the functional intestinal development is essential for the design of optimal treatments ensuring survival and growth of premature infants. The purpose of this study was to evaluate the gene expression profiles of the developing human ileum and colon at mid-gestation. Our results showed that more than 11% of the genes were differentially expressed between ileum and colon. Pathway analysis revealed an even higher level of transcriptional dissimilarity between the developing ileum and the colon including 35% of the significant cellular, molecular and physiological functions and 85% of the canonical pathways. Segment-specific/over-expressed functions in the ileum included a number of amino acid, vitamin and mineral metabolisms and lymphoid tissue structure and development reflecting the high level of maturity of the small intestine as compared to the colon in which cell cycle, cell morphology and actin cytoskeleton, integrin and ERK/MAPK signaling were the predominant functions. All together, functional clustering analysis of the differentially expressed genes revealed important functional difference between the two segments namely to an unexpected relative immaturity of the colon. Two-condition experiment: three human fetal small intestines vs. three human fetal large intestines.
2011-01-01 | E-GEOD-20983 | biostudies-arrayexpress