Expression data from study on IL33 signaling in Dusp5 deficient eosinophils
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE62999 | GEO | 2014/11/06
SECONDARY ACCESSION(S): PRJNA266408
REPOSITORIES: GEO
Similar Datasets
Project description:Dusp5 regulates ERK phosporylation following IL-33 receptor ligation in cultured eosinophils. Dusp5 deficient eosinophils show increased ERK phosphorylation, and as a result are less apoptotic. Since ERK stimulation results in downstream activation of transcription factors, we are utilizing a microarray approach to find alterations in gene expression to uncover potential mechanisms for increased cell survival. Day 12 bone marrow derived eosinophils from Dusp5+/+ and Dusp5-/- mice (5 mice per genotype) were left untreated (media only) or IL-33 (25ng/ml) stimulated for 4 hours. Treated cells were washed with ice cold PBS and cell pellets were directly lysed in RLT buffer (Qiagen) followed by immediate RNA isolation (RNEasy plus mini kit with genomic DNA eliminator columns). Sample group names: Group 1- Dusp5+/+ Untreated (N=5) Group 2- Dusp5-/- Untreated (N=5) Group 3- Dusp5+/+ IL-33 4hrs (N=5) Group 4- Dusp5-/- IL-33 4hrs (N=5) Sample Names: Group 1- BM Eos unstimulated WT-1....WT-5 Group 2- BM Eos unstimulated Dusp5-/- -1......Dusp5-/- -5 Group 3- BM Eos IL-33 4hrs WT-1....WT-5 Group 4- BM Eos IL-33 4hrs Dusp5-/- -1......Dusp5-/- -5
2014-11-06 | E-GEOD-62999 | biostudies-arrayexpress
Project description:Coding RNA expression of blood eosinophils from mepolizumab- or omalizumab-treated patients stimulated ex vivo with IL-33 for 6 hours and of directly processed non-stimulated blood eosinophils from the same samples (paired design)
2021-12-17 | E-MTAB-10189 | biostudies-arrayexpress
Project description:Aim of the experiment was to assess differences in expression of coding RNA between bone marrow eosinophils arising in IL-5 knock-out mice (C57BL/6-Il5tm1Kopf/J) or wild-type littermates and their response to cytokine stimulation. Bone marrow eosinophils were sorted by FACS submitted to RNA-seq immediately or after 4 hours of stimulation with IL-5 and IL-33 in culture plates.
2021-12-17 | E-MTAB-10188 | biostudies-arrayexpress
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
Project description:Eosinophils costimulation with anti-Siglec-F and IL-33 synergistically increases their IL-4 and IL-13 release (Willebrand et al. PLoS One 2016). Here we analyze costimulation induced transcriptional changes involved that potentially enhance effector release.
2021-11-23 | GSE166968 | 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:Memory helper T cells provide long-lasting host defeMemory helper T cells provide long-lasting host defense against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown. We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2hi memory T helper-2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils. Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders. against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown. We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2 hi memory T helper-2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils. Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders.
2018-08-21 | GSE114921 | 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: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
Project description:Depletion of autophagy-associated protein 5 (Atg5), specifically within the eosinophil lineage in mice, resulted in increased body weight, impaired glucose metabolism, and structural alterations in adipose tissue. Our findings highlight that Atg5 influences the functional activity of eosinophils within adipose tissue rather than their quantity. To gain a deeper understanding of the molecular mechanisms underlying ATG5's role in eosinophils, we conducted total RNA-seq analyses on control and Atg5-deficient eosinophils isolated from both bone marrow and blood of mice.
2023-11-21 | GSE245134 | GEO