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Genome-wide analysis of chromatin landscape in murine bone marrow derived eosinophils

ABSTRACT: We applied a global approach using broad-range, next-generation sequecing to identify a repertoire of eosinophil-specific enhancers. H3K4me1, H3K4me3, H3K27ac and PU.1 ChIPseq data was paired with ATAC and gene expression data from bmEos. Transcription factor motif analysis revealed enrichment for PU.1 in eosinophil enhancers, and ChIP-seq confirmed PU.1 binding in enhancer of genes highly expressed in eosinophils. Comparison of identified PU.1-bound enhancers with 3 publically available myeloid datasets (neutrophils, bone marrow derived macrophages and immature granulocytes) revealed 25% of PU.1-bound enhancers were unique to eosinophils - an eosinophil-specific PU.1 regulome. GO analysis of eosinophil-specific PU.1-bound enhancers revealed enrichmend for genes involved in migration, proliferation, degranulation and survival. Collectively, our data identify eosinophil-specific enhancers regulating key eosinophil genes through epigenetic mechanisms and TF binding. These findings are supportive of a dynamic, epigenetic eosinophil regulome underlying eosinophil function and diversity.

ORGANISM(S): Mus musculus

PROVIDER: GSE144951 | GEO | 2021/06/08

REPOSITORIES: GEO

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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

Eosinophils promote lung emphysema via CTSL

Project description:Patients with chronic obstructive pulmonary disease (COPD) having higher blood eosinophil levels exhibit worse lung function and more severe emphysema, implying the potential role of eosinophils in emphysema development. However, the specific mechanism underlying eosinophil-mediated emphysema development is not fully elucidated. In this study, single-cell RNA sequencing was used to identify eosinophil subgroups in mouse models of asthma and emphysema and analyze their functions. Analysis of the accumulated eosinophils revealed differential transcriptomes between the mouse lungs of elastase-induced emphysema and ovalbumin-induced asthma., Eosinophil depletion alleviated elastase-induced emphysema. Notably, eosinophil-derived cathepsin L (CTSL) degraded the extracellular matrix (ECM), causing emphysema in the pulmonary tissue. Eosinophils were positively correlated with serum CTSL levels, which were increased in patients with emphysema than in those without emphysema. Collectively, these results suggest that CTSL expression in eosinophils plays an important role in ECM degradation and remodeling and is related to emphysema in patients with COPD. Therefore, eosinophil-derived CTSL may serve as a potential therapeutic target for patients with emphysema.

2023-10-17 | GSE237749 | GEO

Transcriptional analysis of TREM-1+ and TREM-1- airway eosinophils during allergic inflammation

Project description:Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) an innate receptor that canonically amplifies inflammatory signaling in neutrophils and monocytes, plays a central role in regulating lung inflammation. Utilizing a murine model of asthma, flow cytometry revealed TREM-1+ eosinophils in the lung tissue and airway during allergic airway inflammation. TREM-1 expression was restricted to recruited, inflammatory eosinophils. Expression was induced on bone marrow derived eosinophils by incubation with IL-33, LPS, or GM-CSF. Compared to TREM-1- airway eosinophils, TREM-1+ eosinophils were enriched for pro-inflammatory gene sets including migration, respiratory burst, and cytokine production. Unexpectedly, eosinophil-specific ablation of TREM-1 increased airway IL-5 and lung tissue eosinophil accumulation. Further investigation of transcriptional data revealed apoptosis related gene sets were enriched in TREM-1+ eosinophils. Annexin V staining demonstrated higher rates of apoptosis among TREM-1+ eosinophils compared to TREM-1- eosinophils in the inflammatory airway. In vitro, Trem1/3-/- eosinophils were protected from apoptosis. Finally, inhibition of reactive oxygen species production with diphenyleneiodonium protected WT bone marrow derived eosinophils from apoptosis more than Trem1/3-/- eosinophils, suggesting that superoxide accounted for more apoptosis in WT cells. These data demonstrate protein level expression of TREM-1 by eosinophils for the first time, define a population of TREM-1+ inflammatory eosinophils, and reveal that eosinophil TREM-1 restricts key features of type 2 lung inflammation.

2023-12-15 | GSE246389 | GEO

Expression profiles of sorted murine lung Eosinophils following allergen challenge

Project description:The eosinophil transcriptome analysis indicated a robust transcription change in eosinophils following allergen challenge in the lung. Eosinophils were FACS-sorted from Saline or OVA challenged lung with high purity and then subjected to genome-wide RNA microarray

2014-05-19 | E-GEOD-57757 | biostudies-arrayexpress

Time-course Activation of Human Peripheral Blood Eosinophils by Cytokines

Project description:Activated eosinophils contribute to airway dysfunction and tissue remodeling in asthma, and thus are considered an important factor in asthma pathology. We report here comparative proteomic and phosphoproteomic changes upon activation of eosinophils using eight cytokines individually and in selected cytokine combinations, in time-course reactions. Differential protein and phosphoprotein expressions were determined by mass spectrometry after 2-dimensional gel electrophoresis (2DGE) followed by protein identification by MS, and by label-free LC-MS/MS. We found that each cytokine-stimulation produced significantly different changes in the eosinophil proteome and phosphoproteome, with phosphoproteomic changes being more pronounced and having an earlier onset. Furthermore, we observed that IL-5, GM-CSF, and IL 3 showed the greatest change in protein expression and phosphorylation, and this expression differed markedly from those of the other five cytokines evaluated. Comprehensive univariate and multivariate statistical analyses were employed to evaluate the comparative results. We also monitored eosinophil activation using flow cytometry (FC) analysis of CD69 expression. In agreement with our proteomic studies, FC indicated that IL-5, GM-CSF, and IL-3 were more effective than the other five cytokines studied in stimulating a cell surface CD69 increase indicative of eosinophil activation. Moreover, selected combinations of cytokines revealed proteomic patterns with many proteins in common with single cytokine expression patterns but also showed a greater than additive effect of the two cytokines employed, indicating a more complex signaling pathway that was reflective of a more typical inflammatory pathology.

2017-12-19 | PXD004043 | Pride

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

Metastasis-entrained eosinophils enhance lymphocyte-1 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 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.

2021-08-06 | GSE181491 | GEO

Transcriptomics of circulating human eosinophils

Project description:Global expression pattern in eosinophils in various conditions such as eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Eosinophil were isolated from peripheral blood by FACS from 4 hypereosinophilic conditions: eosinophilic asthma (4 replicates), hypereosinophilic dermatological diseases (3 replicates), parasitosis (3 replicates) and pulmonary aspergillosis (4 replicates).

2015-12-10 | E-GEOD-65239 | biostudies-arrayexpress

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

The impact of eosinophils on the in vitro differentiation of osteoclasts

Project description:To investigate the role of eosinophils on osteoclast differentiation from bone marrow-derived monocytes (BMMs), BMMs were cultivated in the presence or absence of eosinophils and eosinophil supernatant as compared with unstimulated control.

2024-01-09 | GSE203541 | GEO

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