Determine anti-Siglec-F and IL-33 costimulation induced transcriptional changes on murine eosinophils
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE166968 | GEO | 2021/11/23
REPOSITORIES: GEO
Similar Datasets
Project description:Determine anti-Siglec-F and IL-33 costimulation induced transcriptional changes on murine eosinophils
| PRJNA702493 | ENA
Project description:Dr. Paulson's group investigates the roles of carbohydrate-binding proteins involved in immune regulation and human disease, through their interaction with carbohydrate groups expressed on cell surface glycoconjugates. This laboratory is currently focused on how sialoside ligands modulate Siglec functions and on understanding the molecular basis of glycosylation changes following differentiation and activation of leukocytes. Three RNA preparations from IL-5 transgenic C567/B1 adult mouse eosinophils were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to the GLYCOv3 microarrays. Data was analyzed to determine glycosyltransferase expression on mouse eosinophils, with specific interest in a cis-ligand of Siglec-F on eosinophils
2011-04-29 | E-GEOD-28923 | biostudies-arrayexpress
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
Project description:Immunomodulation of mast cell (MC) activity is warranted in allergic and inflammatory diseases where MCs have a central role in pathogenesis. Targeting Siglec-8, an inhibitory receptor on MCs and eosinophils, has shown promising activity in preclinical and clinical studies. While the intracellular pathways that regulate Siglec-8 activity in eosinophils have been well studied, the signaling mechanisms that lead to MC inhibition have not been fully elucidated. Here, we evaluate the intracellular signaling pathways of Siglec‐8‐mediated inhibition in primary MCs using an anti‐Siglec‐8 monoclonal antibody (mAb). Phospho‐proteomic profiling of FcεRI‐activated MCs revealed Siglec-8 mAb-treatment globally inhibited proximal and downstream kinases, leading to attenuated MC activation and degranulation. In fact, Siglec‐8 was found to directly interact with FcεRI signaling molecules. Siglec‐8 inhibition was dependent on both cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that interact with the SH2 containing protein phosphatase Shp-2 upon Siglec-8 phosphorylation. Taken together, these data support a model in which Siglec-8 regulates proximal FcεRI‐induced phosphorylation events through phosphatase recruitment and interaction with FcεRI, resulting in global inhibition of MCs upon Siglec-8 mAb engagement.
2022-01-21 | PXD030820 | Pride
Project description: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.
2018-03-20 | GSE112010 | GEO
Project description:The mechanisms underlying the increased mortality of secondary infections during the immunosuppressive phase of sepsis remain elusive. We established a mouse model of sepsis-induced immunosuppression followed by secondary infection. Compared to other organs, we observed a significant reduction in pro-inflammatory cytokines in the spleen, accompanied by a marked increase in IL-10 production, primarily by infiltrating neutrophils. Furthermore, we confirmed that these infiltrating neutrophils in the spleen during the immunosuppressive phase of sepsis undergo phenotypic change in the local microenvironment, exhibiting high expression of neutrophil biomarkers such as Siglec-F, Ly6G, and Siglec-E. These neutrophils subsequently produced IL-10 to suppress T lymphocytes. Depletion of neutrophils or specifically targeting Siglec-F leads to a notable improvement in the survival of mice with secondary infections. The identification of Siglec-F+ neutrophils as key regulators of immunosuppression following sepsis represents a novel finding with potential therapeutic implications.
2024-04-24 | GSE264139 | GEO
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:Eosinophilia is associated with various persisting inflammatory diseases and often coincides with chronic fungal infections or fungal allergy as in case of allergic bronchopulmonary aspergillosis (ABPA). However, the interactions between eosinophils and fungal pathogen leading to release of inflammatory mediators from eosinophils are poorly understood. Therefore, we established a co-culture system of mouse bone marrow derived eosinophils (BMDE) with Aspergillus fumigatus (Af) that we used in part to analyse transcriptional regulation induced by Af.
2022-05-31 | GSE165694 | GEO
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:Type I interferons are critical anti-viral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The secretion of type I interferon of pDCs is modulated by Siglec-H, a DAP12 associated receptor on pDCs. We showed that Siglec-H deficient pDCs produce more of the type I interferon IFN-α in vitro and that Siglec-H ko mice produce more IFN-α after murine cytomegalovirus (mCMV) infection in vivo, leading to efficient clearance of the virus. Furthermore, ageing Siglec-H ko mice showed a mild form of systemic autoimmunity. In contrast, Siglec-H ko mice developed a severe form of systemic lupus-like autoimmune disease with strong kidney nephritis several weeks after a single mCMV infection. This induction of systemic autoimmune disease after virus infection in Siglec-H ko mice was accompanied by a type I interferon signature and fully dependent on type I interferon signaling. These results show that Siglec-H normally serves as modulator of type I interferon responses after infection with a persistent virus and thereby prevents induction of autoimmune disease. For microarray experiments gene expression profiles of total splenic cells from two wt and Siglec-H ko mice 26 weeks after infection with luciferase expressing murine Cytomegalovirus (5x105 pfu) or from two uninfected wt and Siglec-H ko control mice were analyzed
2016-03-16 | E-GEOD-79248 | biostudies-arrayexpress