GSE128027
Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared to Common Beta-Chain Cytokines IL-5 and GM-CSF
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. Overall design: A total of 28 samples were analyzed (7 eosinophil donors, with each eosinophil collection split and independently subjected to 4 conditions - unstimulated, GM-CSF stimulated, IL-3 stimulated, IL-5 stimuated). RNA-Seq data was mapped against the hg38 reference using TopHat [15] (v1.4.1., --librarytype fr-secondstrand -C) and the RefSeq gene annotation downloaded from the UCSC Genome Browser site.