Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Active eosinophils regulate host defense and immune responses during intestinal inflammation

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE182001 | GEO | 2021/10/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The aryl hydrocarbon receptor partially controls tissue adaptaion of intestinal eosinophils in mice

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

Tissue adaptaion of intestinal eosinophils in mice

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

Single cell RNA Squencing of Human Eosinophils in Allergc Inflammation in the Esophagus

Project description:Eosinophils are elusive cells involved in allergic inflammation. Herein, we profiled 586 human eosinophils from the circulation and an allergic inflammatory site, the esophagus, of patients with eosinophilic esophagitis by Seq-Well–based single-cell RNA sequencing. The esophageal eosinophils were composed of a population of activated eosinophils (enriched in 659 genes compared with peripheral blood-associated eosinophils) and a small population of eosinophils resembling peripheral blood eosinophils (enriched in 62 genes compared with esophageal eosinophils). Esophageal eosinophils expressed genes involved in sensing and responding to diverse stimuli, most notably interferon-Ɣ(IFN-Ɣ), interleukin 10 (IL-10), histamine and leukotrienes, and succinate metabolite signaling. Esophageal eosinophils were most distinguished from other esophageal populations by gene expression of the receptors CCR3, HRH4, SUCNR1, and VSTM1; transcription factors CEBPE, OLIG1, and OLIG2; protease PRSS33; and hallmark eosinophil gene CLC. A web of bidirectional eosinophil interactions with other myeloid cells, T cells, fibroblasts, and the epithelium and vasculature was derived. Comparing esophageal eosinophils and mast cells revealed that esophageal eosinophils expressed genes involved in DAP12 interactions, IgG receptor-triggered events, immunoregulation, and IL-10 signaling, whereas esophageal mast cells expressed genes involved in arachidonic acid metabolism and response to unfolded proteins. These findings indicate that esophageal eosinophils exist as two populations, a minority population resembling blood eosinophils and the other population characterized by high de novo transcription of diverse sensing receptors and inflammatory mediators readying them to intersect with diverse cell types.

2024-08-09 | GSE256088 | GEO

Expression data from small intestinal eosinophils and dendritic cells

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

Small Intestinal Resident Eosinophils Maintain Gut Homeostasis Following Microbial Colonisation

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

Clec4a4+ and Clec4a4- eosinophils in the small intestine

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

Active eosinophils regulate host defense and immune responses during intestinal inflammation

Project description:Active eosinophils regulate host defense and immune responses during intestinal inflammation

| PRJNA754165 | ENA

Propionate axis in infancy small intestinal eosinophils

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

Metastasis-entrained eosinophils enhance lymphocyte-mediated anti-tumor immunity

Project description:The recognition of the immune system as a key component of the tumor microenvironment (TME) led to promising therapeutics. Since such therapies benefit only subsets of patients, understanding the activities of immune cells in the TME is required. Eosinophils are an integral part of the TME especially in mucosal tumors. Nonetheless, their role in the TME and the environmental cues that direct their activities are largely unknown, especially in metastasis. We report that breast cancer-driven lung metastasis is characterized by resident and recruited eosinophils. Eosinophil recruitment to the metastatic lung was regulated by G protein coupled receptor signaling but independent of CCR3. Functionally, eosinophils promoted lymphocyte-mediated anti tumor immunity. Transcriptome and proteomic analyses identified the TME rather than intrinsic differences between eosinophil subsets as a key instructing factor directing anti tumorigenic eosinophil activities. Specifically, TNF-a/IFN-g-activated eosinophils facilitated CD4+ and CD8+ T cell infiltration and promoted anti-tumor immunity. Collectively, we identify a mechanism by which the TME entrains eosinophils to adopt anti-tumorigenic properties, which may lead to the development of eosinophil-targeted therapeutics.

2021-07-27 | PXD027596 | Pride

The neuropeptide neuromedin U directs eosinophils to promote epithelial cell differentiation and barrier immunity of the small intestine

Project description:In this work we show that neuromedin U receptor 1 (NMUR1)-mediated signaling programs SI eosinophils to support epithelial cell differentiation and barrier immunity. The global transcriptional profiling of eosinophils from different tissues of mice revealed that Nmur1 was expressed in a subset of eosinophils specifically in the SI. Fate mapping analyses showed that NMUR1 expression in SI eosinophils was imprinted by local microenvironment and further enhanced by the inflammation. Genetic deletion of NMUR1 decreased the numbers of eosinophils, degranulation activity, and goblet cell differentiation in the SI. Chemogenetic manipulation of NMU-expressing cells significantly altered the goblet cell differentiation and mucus secretion. Eosinophil-organoid co-culture experiments demonstrated that NMU-mediated eosinophil activation directly promoted the growth of intestinal organoids and formation of budding domains and complex crypt–villus structures. Finally, the deficiency of NMUR1 compromised anti-parasite immunity. Thus, NMU regulates epithelial cell differentiation and function through stimulating NMUR1-expressing eosinophils in the SI, highlighting the importance of neuro-immune-epithelium crosstalk in maintaining tissue homeostasis.

2023-09-01 | GSE211112 | 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