Cytokine-induced transcriptional changes in human neutrophils reveal immune regulatory plasticity.

Introduction: Neutrophils are innate immune cells that play a central role in the inflammatory response. They produce an array of destructive molecules and anti-microbial proteases that characterize the cells as front-line defenders, crucial to host defence. It is now appreciated that neutrophils produce and respond to a variety of inflammatory signals and are able to regulate both the innate and adaptive immune responses. However, the mechanisms by which neutrophils respond to different inflammatory signals to regulate their own function and the functions of other immune cells are incompletely defined. Methods: In this study, we performed RNA sequencing of healthy human neutrophils exposed for 1 h to a range of pro-inflammatory cytokines. Results: Granulocyte/macrophage colony-stimulating factor and tumour necrosis factor alpha induced significant changes in 1651 and 693 genes, respectively (adj. Conclusion: This work defines the differential gene expression patterns in neutrophils exposed to different regulatory cytokines. This is important in both increasing our understanding of the role of neutrophils in driving innate and adaptive immune responses and, importantly, for deconvoluting the neutrophil gene expression signatures observed in inflammatory diseases.