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

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. This study aimed to explore the genetic alterations in leukocytes in peripheral blood after ischemia-reperfusion, aiming to discover new biomarkers and potential therapeutic targets. 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 h post-ischemia‒reperfusion. This method integrated genes that exhibited regular changes over time. In this study, we thoroughly analyzed the dynamic changes in gene expression post-IRI, revealing significant enrichment in key signaling pathways that regulate immune responses and T-cell activation over time. Our identification of the interleukin-7 receptor (IL7R) was particularly striking, as it plays a crucial molecular role in IRI. Additionally, using 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. Using KAS-Seq analysis of leukocytes from peripheral blood, we successfully delineated the temporal patterns of gene expression and changes 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 provides innovative avenues for the development of IRI treatments.