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Learn MoreBackground: 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. SOURCE: Pandurangan Vijayanand (vijay@lji.org) - Vijayanand Lab La Jolla Institute for Immunology
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