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Transcriptional profiling of eosinophil subsets in Interleukin-5 transgenic mice

ABSTRACT: Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. Interleukin-5 (IL-5) is a critical regulator of eosinophil development, controlling proliferation, differentiation and maturation of the lineage. Mice that constitutively express IL-5 have more than 10 fold more eosinophils in the haematopoietic organs than their wild type counterparts. We have identified that much of this expansion is in a population of Siglec-F high eosinophils, which are rare in wild type mice. In this study we assessed transcription in myeloid progenitors, eosinophil precursors and Siglec-F medium and Siglec-F high eosinophils from IL-5 transgenic mice and in doing so have created a useful resource for eosinophil biologists. We have then utilised these populations to construct an eosinophil trajectory based on gene expression and to identify gene sets that are associated with eosinophil lineage progression. Cell cycle genes were significantly associated with the trajectory, and we experimentally demonstrate an increasing trend towards quiescence along the trajectory. Additionally we found gene expression changes associated with constitutive IL-5 signalling in eosinophil progenitors, many of which were not observed in eosinophils.

ORGANISM(S): Mus musculus

PROVIDER: GSE112010 | GEO | 2018/03/20

REPOSITORIES: GEO

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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

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

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

PIR-B negatively regulates IL-13-induced esophageal eosinophil effector functions

Project description:Eosinophilic esophagitis (EoE) is a T helper type 2 (TH2) cytokine-associated disease charaterized by eosinophil infiltration, epithelial cell hyperplasia and tissue remodeling. Recent studies have highlighted a major contribution for IL-13 in EoE pathogenesis. Paired immunoglobulin-like receptor (PIR)-B is a cell surface immune-inhibitory receptor that is expressed by eosinophils and postulated to regulate eosinophil development and migration. We report that Pirb is upregulated in the esophagus after inducible overexpression of IL-13 (CC10-IL13 Tg mice) and is overexpressed by esophageal eosinophils. CC10-IL13Tg/PirB-/- mice displayed increased esophageal eosinophilia and EoE pahtology, including epithelial cell thickening, fibrosis and angiogenesis, compared with CC10-IL13 Tg/PirB+/+ mice. Transcriptome analysis of primary Pirb+/+ and Prib-/- esophageal eosinophils revealed increased expression of transcripts associated with promoting tissue remodeling in Pirb-/- eosinophils including pro-fibrotic genes, genes promoting epithelial-to-mesenchymal transition (EMT) and genes associated with epithelial growth. These data identify PIR-B as a molecular checkpoint in IL-13-induced eosinophil accumulation and activation, which may serve as a novel target for future therapy in EoE.

2016-05-05 | GSE81135 | GEO

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

2013-08-01 | GSE43660 | GEO

Eosinophil-derived IL-4 promotes nematode growth in an innate context

Project description:It has become increasingly clear in recent years that the function for eosinophils in health and disease is highly varied. Recent studies have revealed novel functions for eosinophils in metabolism and tissue regeneration. Such mechanisms have strong potential to be relevant in worm infections in which parasites rely on host metabolism for nutrients that support worm growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that normal larval growth requires IL-4 and STAT6 signaling that are intrinsic to eosinophils. Support of growth by eosinophil-derived IL-4 occurs independently of adaptive immunity. Host gene expression in skeletal muscle was compatible with a regenerative response to invasion by newborn larvae and a shift in the source of energy in infected tissue. Furthermore, the presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4) and phosphorylation of Akt were observed in nurse cells, compatible with enhancement of glucose uptake and storage of glycogen by larvae that is known to occur. The results suggest that eosinophil-derived IL-4 may promote larval growth by altering nutrient metabolism in infected muscle. Our findings document a novel interaction between worms and host, in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth. Whole diaphragms from WT, Rag1-/- and PHIL mice were harvested at 0, 2 and 7 days post-infection of mice with 25,000 Trichinella spiralis newborn larvae (administered retro-orbitally) and preserved in RNAlater (Qiagen). Two to three replicate mice were used for each condition.

2015-07-10 | E-GEOD-67136 | biostudies-arrayexpress

Gene expression analyses and distribution of H3K4me3 modification during eosinophil development (GMP to EoP to Eosinophil)

Project description:To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global approach to identify genome-wide transcriptome and epigenome changes that occur during homeostasis at critical developmental stages, including eosinophil-lineage commitment (eosinophil progenitor [EoP] compared to granulocyte-monocyte progenitor [GMP]) and lineage maturation (eosinophil compared to EoP). Our analyses revealed markedly greater transcriptome alterations associated with eosinophil maturation (1199 genes) compared to eosinophil-lineage commitment (490 genes), highlighting the greater transcriptional investment necessary for differentiation. Our analyses also delineated a 976 gene eosinophil-lineage transcriptome that included a repertoire of 56 transcription factors, many of which have never previously been associated with eosinophils. Epigenomic studies revealed that genes that were specifically induced with eosinophil-lineage commitment in EoPs were “poised” with active chromatin marks in GMPs, despite not being expressed in GMPs. In contrast, a majority of the genes that were highly and specifically induced with maturation in eosinophils was not associated with poised chromatin, suggesting distinct epigenetic regulation between genes induced with lineage commitment compared to genes induced with cell maturation during eosinophil development.

2015-08-13 | GSE69707 | GEO

Nutrient-derived signals regulate eosinophil adaptation to the small intestine

Project description:Eosinophils are commonly regarded as effector cells of type 2 immunity, yet they also accumulate in certain tissues during homeostasis - particularly in the gastrointestinal tract. Our understanding of the processes that govern homeostatic eosinophil accumulation and tissue-specific adaptation, and their functional significance, remains very limited. Here, we investigated how eosinophils adapt to the small intestine microenvironment and the local signals that regulate this process. We observed that eosinophils gradually migrate up the crypt-villus axis, giving rise to a villus-resident subpopulation with a distinct transcriptional signature. Genetic deficiency of eosinophils resulted in a reduction of villus area, as well as a reduction of multiple other immune cell populations, demonstrating their diverse functions in this environment. We determined that retinoic acid receptor signaling is specifically required for the maintenance of villus-resident eosinophils, while IL-5 is largely dispensable outside of its canonical role in eosinophil production. In addition, we unexpectedly found that high protein diet suppresses the accumulation of villus-resident eosinophils. Purified amino acids were sufficient for this effect, which was a consequence of accelerated eosinophil turnover within the tissue microenvironment and not due to altered development in the bone marrow. Our study provides new insight into the process of eosinophil adaptation to the small intestine and its dependence on nutrient-derived signals.

2024-01-16 | GSE236132 | GEO

Microarray analysis on RNA from lung eosinophil subpopulation from naive or HDM-treated mice using Affymetrix Mouse Gene 2.0 ST

Project description:As opposed to their well-characterized contributions to inflammatory processes, tissue eosinophils are now also thought to contribute to immune homeostasis at mucosal sites such as the gut. Yet, whether such steady-state eosinophils exist in the lung is currently unclear. In this project, we identified and characterized lung resident eosinophil and also studied what happen to these cell during a mouse model of allergic inflammation (House dust mite (HDM) exact administrations). We compared the transcriptional profile of lung resident eosinophil from naive mice (rEOS ss) or from HDM-treated mice (rEOS i) and of inflammatory eosinophil (iEOS) from HDM-treated mice.

2016-06-07 | E-MTAB-4084 | biostudies-arrayexpress

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