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Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared to Common Beta-Chain Cytokines IL-5 and GM-CSF

ABSTRACT: Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared to Common Beta-Chain Cytokines IL-5 and GM-CSF

PROVIDER: PRJNA526069 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8698120.fastq.gz	Fastqsanger.gz
	SRR8698130.fastq.gz	Fastqsanger.gz
	SRR8698140.fastq.gz	Fastqsanger.gz
	SRR8698150.fastq.gz	Fastqsanger.gz
	SRR8698160.fastq.gz	Fastqsanger.gz

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Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared to Common Beta-Chain Cytokines IL-5 and GM-CSF

Project description:Background: Despite recent advances in asthma management with anti-IL-5 therapies, many patients with eosinophilic asthma remain poorly controlled. IL-3 shares a common beta subunit receptor with both IL-5 and GM-CSF, but through alpha subunit-specific properties, uniquely influences eosinophil biology and may serve as a potential therapeutic target. Objective: We aimed to globally characterize the transcriptomic profiles of GM-CSF, IL-3, and IL-5 stimulation and identify differences in gene expression using advanced statistical modeling. Methods: Human eosinophils were isolated from the peripheral blood of healthy volunteers and stimulated with either GM-CSF, IL-3 or IL-5 for 48 hours. RNA was then extracted and bulk sequencing performed. DESeq analysis identified differentially expressed genes and weighted gene co-expression network analysis independently defined modules of genes that are highly co-expressed. Results: IL-3 stimulation yielded the most numbers of differentially expressed genes that were also highly co-expressed. GM-CSF and IL-5 stimulation demonstrated redundancy in eosinophil gene expression. Conclusion: IL-3 produces a distinct eosinophil gene expression program among the beta-chain receptor cytokines.

2019-09-06 | GSE128027 | GEO

Gene expression analysis of cultured bone marrow-derived eosinophils in response to GM-CSF and IL-10 stimulation

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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.

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The Cytokines IL-21 and GM-CSF have Opposing Regulatory Roles in the Apoptosis of Conventional Dendritic Cells

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The Cytokines IL-21 and GM-CSF have Opposing Regulatory Roles in the Apoptosis of Conventional Dendritic Cells

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Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared with Common β-Chain Cytokines IL-5 and GM-CSF.

Project description:Despite recent advances in asthma management with anti-IL-5 therapies, many patients have eosinophilic asthma that remains poorly controlled. IL-3 shares a common β subunit receptor with both IL-5 and GM-CSF but, through α-subunit-specific properties, uniquely influences eosinophil biology and may serve as a potential therapeutic target. We aimed to globally characterize the transcriptomic profiles of GM-CSF, IL-3, and IL-5 stimulation on human circulating eosinophils and identify differences in gene expression using advanced statistical modeling. Human eosinophils were isolated from the peripheral blood of healthy volunteers and stimulated with either GM-CSF, IL-3, or IL-5 for 48 h. RNA was then extracted and bulk sequencing performed. DESeq analysis identified differentially expressed genes and weighted gene coexpression network analysis independently defined modules of genes that are highly coexpressed. GM-CSF, IL-3, and IL-5 commonly upregulated 252 genes and downregulated 553 genes, producing a proinflammatory and survival phenotype that was predominantly mediated through TWEAK signaling. IL-3 stimulation yielded the most numbers of differentially expressed genes that were also highly coexpressed (n = 119). These genes were enriched in pathways involving JAK/STAT signaling. GM-CSF and IL-5 stimulation demonstrated redundancy in eosinophil gene expression. In conclusion, IL-3 produces a distinct eosinophil gene expression program among the β-chain receptor cytokines. IL-3-upregulated genes may provide a foundation for research into therapeutics for patients with eosinophilic asthma who do not respond to anti-IL-5 therapies.

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Project description:Gene expression analysis of cultured bone marrow-derived eosinophils in response to GM-CSF and IL-10 stimulation

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