Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Metastasis-entrained eosinophils enhance lymphocyte-1 mediated anti-tumor immunity

ABSTRACT: 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 anti53 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE181491 | GEO | 2021/08/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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

Eosinophil specific transcriptome in homeostatic intestine and lung

Project description:Objective: To study the physiological role of eosinophils in the GI tract and lung under homeostatic conditions, Method: we analyzed tissue-specific eosinophil gene expression patterns by genome-wide expression microarray analysis using RNA isolated from FACS-sorted eosinophils from the small intestine or lung of naive BALB/cmice (Live eosinophils were identified as DAPI-CCR3+Siglec-F+CD45+CD4-CD8a-CD19-B220-SSChigh cells). Result: There are 513 genes that are differentially expressed by intestinal eosinophils and Lung eosinophils. Conclusion: Eosinophils from different tissues have unique gene expression patterns for distinct functions. we analyzed tissue-specific eosinophil gene expression patterns by genome-wide expression microarray analysis using RNA isolated from FACS-sorted eosinophils from the small intestine or lung of naive BALB/cmice (Live eosinophils were identified as DAPI-CCR3+Siglec-F+CD45+CD4-CD8a-CD19-B220-SSChigh cells).

2011-11-23 | E-GEOD-33807 | biostudies-arrayexpress

Eosinophil specific transcriptome in homeostatic intestine and lung

2011-11-23 | GSE33807 | GEO

Analysis of eosinophil maturation and activation

Project description:The study compares the gene expression associated with maturation and activation of murine eosinophils. Immature (CCR3-) and mature (CCR3+) eosinophils isolated from the bone marrow were compared; and activated eosinophils isolated from the lung of Nippostrongylus brasiliensis infected mice were compared to resting eosinophils isolated from the spleen of IL-5 transgenic mice. Keywords: cellular differentiation comparison

2006-12-30 | GSE5411 | GEO

Mouse resident lung eosinophils are dependent on IL-5

Project description:Purpose: we aimed to characterized eosinophils in the murine model of asthma Methods: Eosinophils were sorted from the lung of naïve and and HDM-induced asthma mice. There after RNA was extracted from the sorted eosinophils and subjected to RNAseq. Results:we demonstrated that resident lung eosinophils require IL-5 for their survival and that the expression of Siglec-F, is regulated by IL-5 . Conclusion: Our data suggest that the distinct eosinophil populations in the asthmatic lung represent a continuum of activation states rather than distinct eosinophil subsets.

2023-04-17 | GSE203225 | GEO

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

IL-33 markedly induces murine eosinophil gene transcription via autocrine IL-4-dependent and -independent mechanisms

Project description:Eosinophils are major effector cells in type 2 inflammatory responses and become activated in response to IL-4 and IL-33, yet the molecular mechanism remains unclear. We examined the direct effect of these cytokines on eosinophils and demonstrated that murine eosinophils respond to IL-4 and IL-33 by phosphorylation of STAT-6 and NFkB, respectively. RNA sequencing analysis of murine eosinophils indicated that IL-33 regulates 519 genes, whereas IL-4 regulates only 28 genes, including 19 IL-33-regulated genes. Interestingly, IL-33 induced eosinophil activation via two distinct mechanisms, IL-4 independent and IL-4 secretion/auto-stimulation dependent. Anti-IL-4 or anti-IL-4Ra antibody-treated eosinophils, as well as Il4- or Stat6-deficient eosinophils, had attenuated protein secretion of a subset of IL-33-induced genes, including Retnla and Ccl17. However, the induction of most IL-33-regulated transcripts (e.g. Il6 and Il13) was IL-4 independent and blocked by NFkB inhibition. Indeed, IL-33 induced the rapid release of pre-formed IL-4 protein from eosinophils by an NFkB-dependent mechanism. Thus, we have identified a novel activation pathway in murine eosinophils that is induced by IL-33 and differentially dependent upon IL-4. These data suggest that IL-4 plays a critical role in auto-amplification of IL-33-induced eosinophil activation and could be a potential target for therapeutic approaches in IL-33-related eosinophil-associated diseases. Low density bone marrow derived murine eosinophils were generated in culture over the period of 14 days. Eosinophils were activated by either IL-33 or IL-4 at 10 ng/ml for 1hr and 4hr. RNA was collected and subjected to next generation sequencing.

2013-08-01 | E-GEOD-43660 | biostudies-arrayexpress

A protective role for eosinophils in host resistance to Mycobacterium tuberculosis

Project description:Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis (TB) are incompletely understood. Here we show a role for eosinophils in host resistance to Mtb infection. In humans, eosinophils are found in resected human TB lung lesions and autopsy granulomas. Eosinophils are also found in granulomas in zebrafish, mice, and non-human primates, where they are functionally activated and degranulate. Transcriptional profiling of lung tissue after Mtb infection of mice, that selectively lack eosinophils, revealed changes in neuronal associated pathways. Importantly, employing several independent models of eosinophil deficiency in mice, we demonstrate that eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings establish an unexpected role for eosinophils, granulocytes typically associated with type II inflammation, in host resistance against Mtb, a major human bacterial pathogen.

2021-08-01 | GSE165871 | GEO

Segmental Allergen Challenge Regulates Gene Expression In Bronchoalveolar Lavage (BAL) Cells From Atopic and Mild Asthmatic Subjects

Project description:Segmental allergen challenge increases the percentage of eosinophils in bronchoalveolar lavage (BAL) cells. Mepolizumab, an anti-IL-5 therapeutic antibody, decreases the number of eosinophils in bronchoalveolar lavages (BAL). The use of both procedures allows to define genes that are either expressed by eosinophils or dependent on eosinophil presence in the airways.

2013-05-01 | GSE46159 | GEO

Differential expression of Triggering Receptor Expressed on Myeloid Cells (Trem)-2 in tissue eosinophils

Project description:No longer regarded as simply end-stage cytotoxic effectors, eosinophils are now recognized as complex cells with unique phenotypes that develop in response to the local microenvironment. In our previous study, we documented eosinophil infiltration in association with characteristic muscle damage in the dystrophin-deficient (mdx) mouse model of Duchenne muscular dystrophy. In this earlier study, we found that eosinophils did not promote formation of muscle lesions, as these persisted in eosinophil-deficient mdx.PHIL mice. To obtain additional insight into these findings, we performed RNA sequencing on eosinophils isolated from muscle tissue of mdx, IL5tg, and mdx.IL5tg mouse strains. We discovered profound up-regulation of classical eosinophil effector proteins (major basic protein-1, eosinophil peroxidase, and eosinophil-associated ribonucleases, or RNases) in eosinophils isolated from lesion-free muscle from IL5tg mice. By contrast, we observed significant upregulation of tissue remodeling genes, including proteases, extracellular matrix components, collagen, and skeletal muscle precursors, as well as the immunomodulatory receptor, TREM2, in eosinophils isolated from skeletal muscle tissue from the dystrophin-deficient mdx mouse strain. The anti-inflammatory properties of TREM2 have been described in the monocyte/macrophage lineage; however, there are no previous studies documenting TREM2 expression in eosinophils. Here we show that TREM2 is critical for full growth and differentiation of bone marrow-derived eosinophil cultures and for full expression of toll-like receptor 4. Immunoreactive TREM2 was also detected on human eosinophils at levels that correlated with donor body mass index. Taken together, our findings provide important insight into the immunomodulatory and remodeling capacity of mouse eosinophils and the flexibility of their gene expression profiles in vivo.

2021-09-27 | GSE158666 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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