Genome-wide KAS-Seq mapping of leukocytes in ischemia-reperfusion model reveals IL7R as a potential therapeutic target for ischemia-reperfusion injury

Background Ischemia‒reperfusion injury (IRI) is one of the leading causes of mortality and disability worldwide. Owing to its complex pathogenesis, there is still a lack of effective therapeutic targets in clinical practice, and exploring the mechanism and targets of IRI is still a major clinical challenge. Objective(s): The goal of this study was to explore the genetic alterations that cause leukocytes in peripheral blood after ischemia‒reperfusion to discover new biomarkers and potential therapeutic targets. Study Design: KAS-Seq (Kethoxal-assisted single-strand DNA sequencing) was used to obtain gene expression profiles of circulating leukocytes in a porcine ischemia‒reperfusion model at 24, 48, and 72 hours after ischemia‒reperfusion, which integrated genes that exhibited regular changes over time. Results In this study, we thoroughly analyzed the dynamic changes in gene expression post-IRI, revealing changes that were significantly enriched in key signaling pathways regulating immune responses and T-cell activation over time. Particularly striking was our identification of the interleukin-7 receptor ( IL7R ), which plays a crucial molecular role in IRI. Additionally, via database mining technology, we confirmed the close relationship between IL7R and IRI, explored the interaction between interferon-γ ( IFNG ) and IL7R in T-cell activation, and clarified their joint influence on ischemia‒reperfusion injury. Conclusions Utilizing KAS-Seq analysis of leukocytes from peripheral blood, we successfully delineated the temporal patterns of gene expression and alterations in signal transduction pathways in porcine models of ischemia‒reperfusion. Subsequent in-depth analysis identified IL7R as a potential novel therapeutic target for IRI. The pivotal role of this gene in modulating immune responses offers innovative avenues for the development of IRI treatments.