Propionate axis in infancy small intestinal eosinophils
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PROVIDER: PRJNA856863 | ENA |
REPOSITORIES: ENA
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Project description:Evidence has accumulated that gut microbiota and its metabolites, in particular, a short chain fatty acid propionate, are significant contributors to the pathogenesis of a variety of diseases, although little is known regarding its impact on pediatric bronchial asthma, one of the most common allergic diseases in childhood. This study aimed to elucidate whether, and if so how, intestinal propionate during lactation is involved in the development of BA. In order to perform a bias-free and comprehensive genetic screening of intestinal eosinophils, we next performed RNA sequencing analysis on SILP eosinophils sorted from offspring mice of mothers fed with propionate-containing water or control water
2022-07-11 | GSE207711 | GEO
Project description:Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. We performed a global gene expression analysis to examine which genes are highly expressed by small intestinal eosinophils (CD11b+CD11c(int)MHCII-SiglecF+) compared with dendritic cells (CD11c+MHCII+).
2016-02-04 | GSE77545 | GEO
Project description:To determine how eosinophils adapt to the intestinal environment, eosinophils were sorted from the bone marrow and small intestine and compared by RNA sequencing. We show here that intestinal eosinophils were specifically adapted to their environment and underwent substantial transcriptomic changes. Intestinal eosinophils upregulated genes relating to the immune response and cell-cell communication, extracellular matrix components and metalloproteases, and the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with broad functions in intestinal homeostasis.
2022-02-25 | GSE185070 | GEO
Project description:Intestinal homeostasis following postnatal microbial colonization requires the coordination of multiple processes, including the activation of immune cells, cell-cell communication, the controlled deposition of extracellular matrix, and epithelial cell turnover and differentiation. The intestine harbors the largest frequency of resident eosinophils of all homeostatic organs, yet the functional significance of eosinophil residence in the gut remains unclear. Eosinophils are equipped to both respond to, and modify, their local tissue environment and thus are able to regulate the adaption of tissues to environmental changes. We report a critical role for eosinophils in regulating villous structure, barrier integrity and motility in the small intestine. Notably, the microbiota was identified as a key driver of small intestinal eosinophil activation and function. Collectively our findings demonstrate a critical role for eosinophils in facilitating mutualistic interactions between host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.
2023-04-01 | GSE201355 | GEO
Project description:To determine how AHR affects eosinophil adaptation to the intestinal environment, eosinophils were sorted from the small intestine from WT, Ahr knockout and Ahrr knockout mice and compared by RNA sequencing. The canonical AHR pathway was active in murine intestinal eosinophils and limited eosinophil survival in the small intestine in a cell-intrinsic manner. Eosinophils from AHR-deficient mice retained increased expression of pathways associated with bone marrow eosinophils and failed to fully express the intestinal gene expression program, including extracellular matrix organization and cell junction pathways. Thus, our study demonstrates that the response to environmental triggers via AHR shapes tissue adaptation of eosinophils in the small intestine.
2022-02-25 | GSE173831 | GEO
Project description:Next generation sequencing was performed to conprehensively investigate the changes of gene expression of small intestinal eosinophils of mice after stimulation with GM-CSF in vitro.
2016-04-30 | GSE56786 | GEO
Project description:Eosinophils contribute to parasitic helminths- and allergens-induced type 2 immune responses. Although the gastrointestinal tract harbors a substantial number of eosinophils, the pathophysiological roles of intestinal eosinophils remain unclear. Here we identify a novel subset of eosinophil that expresses a repertoire of inhibitory molecules, including Clec4a4 and PD-L1. These Clec4a4+ leukocytes are blood-derived and exclusively present in the small intestine. Accordingly, this subset acquires imprinted features by the instruction of AHR signaling, which modulates immune responses to establish gut homeostasis. Selective depletion of AHR in eosinophils leads to a marked reduction of Clec4a4+PD-L1+ eosinophils and enhances the worm clearance accompanied by an increased type 2 immune response. Our findings may open new therapeutic avenues on primary eosinophilic gastrointestinal disorders.
2022-03-25 | GSE199370 | GEO
Project description:In the past decade, single-cell transcriptomics has helped uncover new cell types and states and led to the construction of a cellular compendium of health and disease1. Still, some difficult-to-sequence cell types remain absent from cell atlases. Eosinophils, elusive granulocytes implicated in a plethora of human pathologies2,3, are among these uncharted cell types. To date, the heterogeneity of eosinophils and the gene programs underpinning their pleiotropic functions remain poorly understood4. In the present study, we provide the first comprehensive single-cell transcriptomic profiling of murine eosinophils. We identify an active and a basal population of intestinal eosinophils, differing in their transcriptome, surface proteome and spatial localization. By means of genome wide CRISPR inhibition screen and functional assays, we dissect a mechanism by which IL-33 and IFN-? induce active eosinophil accumulation in the inflamed colon. Active eosinophils are endowed with bactericidal and T cell regulatory activity, and express the co-stimulatory molecules CD80 and PD-L1. Notably, active eosinophils are enriched in the lamina propria of a small cohort of inflammatory bowel disease patients and tightly associate with CD4+ T cells. Our findings provide novel insights into the biology of this elusive cell type and highlight its crucial contribution to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.
2021-10-22 | GSE182001 | GEO
Project description:Tissue adaptaion of intestinal eosinophils in mice
| PRJNA767596 | ENA
Project description:Genes encoding transcription factors function as hubs in gene regulatory networks because they encode DNA-binding proteins, which bind to promoters that carry their binding sites. In the present work we have studied gene regulatory networks defined by genes with transcripts belonging to different mRNA abundance classes in the small intestinal epithelial cell. The focus is the rewiring that occurs in transcription factor hubs in these networks during the differentiation of the small intestinal epithelial cell while it migrates along the crypt-villus axis and during its development from a fetal endodermal cell to a mature adult villus epithelial cell. We have generated transcriptome data for mouse small intestinal villus, crypt and fetal intestinal epithelial cells. In addition we have generated metabolome data from crypt and villus cells. Our results show that the intestinal crypt transcription factor hubs that are rewired during differentiation are involved in the cell cycle process (E2F, NF-Y) and stem cell maintenance (c-Myc). In contrast the villi are dominated by a HNF-4 villus hub, which is rewired during differentiation by the addition of network genes with relevance for lipoprotein synthesis and lipid absorption. Moreover, we have identified a villus NF-kB hub, which was revealed by comparison of the villus and endoderm transcriptomes. The rewiring of the NF-kB villus hub during intestinal development reflects transcriptional activity established by host and microflora interactions. To aid in the mining of our results we have developed a web portal (http://gastro.imbg.ku.dk/mousecv/) allowing easy linkage between the transcriptomic data, biological processes and functions. Experiment Overall Design: Four different sample categories were analyzed. Experiment Overall Design: 1) Small intestinal crypts isolated form 12-weeks old C57BL/6 mice. These samples are in triplicates. Experiment Overall Design: 2) Small intestinal villi isolated form 12-weeks old C57BL/6 mice. These samples are in triplicates. Experiment Overall Design: 3) Embryonic day 12 mesenchyme. These samples are in quadruplicate. each sample is derived from a pool of mesenchymes (10-40) Experiment Overall Design: 4) Embryonic day 12 endoderm. These samples are in quadruplicate. each sample is derived from a pool of endoderms (10-40)
2008-06-12 | E-GEOD-3216 | biostudies-arrayexpress