Identification of novel activation marker and regulator of human basophils via transcriptomic analysis of IL-3-stimulated basophils
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PROVIDER: PRJNA602738 | ENA |
REPOSITORIES: ENA
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Project description:Human basophils regulate allergic immune responses by releasing histamine and effector cytokines such as interleukin 4 (IL-4) and IL-13. IL-3/IL-3R signaling axis plays key roles in the maturation, survival and activation of basophils. We and others have shown that IL-3-induced surface receptors e.g. ST2 and IL-17RB regulate the biology of basophils. We in this study aim to identify new basophil activation maker and regulator by transcriptomic analysis of IL-3-stimulated basophils.
2021-01-01 | GSE144096 | GEO
Project description:Basophils are the least common granulocytes which represent less than 1% of peripheral blood leukocytes. Recent development of analytical tools for basophils enables us to understand their critical roles in allergic reactions and protection from parasitic infections. Nevertheless, the differentiation trajectory of basophils remains unclear. We have identified previously-unappreciated pre-basophil subpopulation which encompasses previously-defined basophil precursors (BaPs) in a series of experiments including scRNA-seq analysis (deposited to GSE206589). In this study, we explored gene expression profiles of pre-basophils and mature basophils activated by antigen/IgE-stimulation or IL-3-stimulation. We have revealed that IL-3 activated pre-basophils displayed distinct gene expression profiles from antigen/IgE- or IL-3-stimulated mature basophils, suggesting the unuque property of pre-basophils.
2023-03-21 | GSE222701 | GEO
Project description:In this study, we explored gene expression profiles of bone marrow-derived basophils stimulated with either IL-3 or control PBS.
2023-03-21 | GSE206593 | GEO
Project description:In this study, we explored gene expression profiles of IL-3+IL-33-stimulated BMBAs treated with difamilast, a highly selective PDE4B inhibitor. We identified that difamilast-treated basophils showed downregulated expression of inflammaory mediators including Il4, Il6 and Il13.
2023-10-11 | GSE234541 | GEO
Project description:Basophils are important effector cells in allergic inflammation, anti-parasitic immune response and skin disorders. A number of activators including interleukin 3 (IL-3) and IgE have been identified in the regulation of human basophils expressing mediators such as histamine and leukotriene C4 (LTC4) and cytokines, including IL-4 and IL-13. Human basophils express high levels of IL-2 receptors. However, the function of the IL-2 pathway in basophils remains unknown. Here, we identify that IL-2-stimulated human basophils in vitro express a variety of inflammatory cytokines and chemokines including IL-5, IL-13, GM-CSF and CCL-17. Of note, one of the top regulated cytokines, IL-5, was for the first time identified to be expressed in human basophils and was distinctly regulated by IL-2, independently of IL-3 and IgE. Immunofluorescence analysis of skin specimens from bullous pemphigoid and eczema revealed that infiltrating basophils in skin lesions widely express IL-5 and GM-CSF. Together, our findings reveal IL-2 as a novel regulator of human basophils to express IL-5 and GM-CSF in skin disorders. This adds a new layer to support the importance of basophils in skin disorders.
2018-10-01 | GSE74375 | GEO
Project description:In this study, we explored gene expression profiles of mature and immature basophils from either IL-3-elicited or TSLP-elicited BMBAs. We revealed that TSLP-elicited mature basophils displayed gene expression profile similar to that of IL-3-elicited mature rather than immature basophils.
2023-03-21 | GSE206592 | GEO
Project description:To investigate the mechanisms by which C/EBPa drives basophil differentiation and maintains basophil identity, we examined whether or not C/EBPa promotes basophil molecular programming and simultaneously represses mast cell molecular programming. We performed genome-wide gene expression profiling on basophils and mast cells and found that 6798 genes were shared by mast cells and basophils; 2033 genes were expressed 2-10 (log2 1-3.3)-fold higher in basophils (differentially expressed in basophils); and 413 genes were expressed greater than 10 (log2 3.3)-fold in basophils (highly expressed in basophils). On the other hand, we found 569 genes were expressed 2-10 (log2 -1 to -3.3) fold higher in mast cells and 171 genes were highly expressed in mast cells [greater than 10 fold (log2 -3.3)]. We treated purified basophils prepared from Cebpaf/f RosaYFP/creER mice and Cebpa+/+ RosaYFP/creER control mice with or without 4HT treatment for five days. Gene expression in the treated basophils was analyzed using microarray analysis. Overall, deletion of C/EBPa in basophils resulted in a reduction of mRNA expression for 248 genes and led to an increase in mRNA expression for 255 genes. The majority of the C/EBPa-regulated genes were either differentially or highly expressed in basophils or mast cells. In this study, we compared gene expression in basophils and mast cell and identified genes which specifically expressed in basophils and mast cells. By using Cebpa conditional knock out mice, we identified Cebpa regulated genes in basophils.
2013-04-01 | E-GEOD-41596 | biostudies-arrayexpress
Project description:Mast cells and basophils are developmentally related cells whose activation is a hallmark of allergy. Functionally, mast cells and basophils overlap in their ability to produce several mediators, including histamine and granule proteases, but studies have increasingly demonstrated non-redundant roles. To characterize the transcriptional heterogeneity of mast cells and basophils upon their activation, we performed large-scale comparative microarrays of murine bone marrow–derived mast cells (BMMCs) and basophils (BMBs) at rest, upon an adaptive-type activation (IgE crosslinking), or upon an innate-type activation (IL-33 stimulation). Hierarchical clustering demonstrated that BMMCs and BMBs shared specific activation-associated transcriptional signatures but differed in others, both between cell type and between activation mode. In BMMCs, IgE crosslinking upregulated 785 genes including Egr2, Ccl1, and Fxyd6, while IL-33 stimulation induced 823 genes including Ccl1, Egr2, and Il1b. Focused bioinformatics pathway analysis demonstrated that IgE activation aligned with processes such as oxidative phosphorylation, angiogenesis, and the p53 pathway. The IL-33–activated transcriptome was enriched in genes commonly altered by NF-B in response to TNF, by IL-6 via STAT3, and in response to IFN. Furthermore, BMBs activated via IgE crosslinking selectively induced immune response genes Ccl1, Il3, and Il2 compared to IL-33–stimulated BMBs. Principal-component analysis revealed key cell- and activation-specific clustering. Overall, our data demonstrate that mast cells and basophils have cell- and activation-specific transcriptional responses and suggest that context-specific gene networks and pathways may shape how the immune system responds to allergens and innate cytokines.
2017-03-17 | GSE96696 | GEO
Project description:It has been previously shown that airway exposure to Toll-like receptor ligands through lipopolysaccharide (LPS)-contaminated house dust or bacterial infections can exacerbate allergic inflammation; however, the underlying mechanism(s) controlling this response have not been fully elucidated. Here we report that basophils are the major source of Th2 cytokines that respond to TLR4 ligands, such as LPS and lipid A, in human PBMC and murine spleen cells. LPS activated human PBMCs to up-regulate mRNAs for not only pro-inflammatory cytokines such as IL-6 and chemokines such as CXCL8 (IL-8), CCL2 (MCP-1), but also Th2 cytokines such as IL-4 and IL13. Among PBMCs, we identified CD123+/BDCA4- basophils as the major source of IL-4 and IL-13 in response to LPS. Even in the absence of IgE, purified human basophils, as well as a basophilic cell line, were directly activated by LPS to produce IL-4 and IL-13. Moreover, LPS-stimulated IL-4 knockin mouse (4get mice) spleens identified the basophils as the major IL-4 producing cells in a TLR4-dependent manner. These results indicate that bacterial LPS may play a role in type-2 immunity through direct activation of basophils to produce IL-4 and IL-13. Keywords: Cell type comparison
2013-12-31 | GSE8589 | GEO
Project description:We performed large-scale comparative microarrays of bone marrow -derived mast cells and basophils at rest, upon an adaptive-type action (IgE-crosslinking) or upon innate-type activation (IL-33-activation).
2017-03-17 | GSE96694 | GEO