Single-cell RNA sequencing analysis of lung tissue profiles of mice undergoing hepatic ischemia-reperfusion

Ischemia-reperfusion(IR) injury is an unavoidable complication during liver transplantation(LT). Acute lung injury (ALI) is the main factor that primarily affects patient survival and post-transplant morbidity and mortality, as the susceptibility of the lungs to reperfusion injury increases significantly during the transplantation process.To assess the phenotype and plasticity of various cell types in the lung tissue microenvironment after hepatic ischemia-reperfusion(HIR) at the single-cell level, we performed single-cell RNA sequencing (scRNA-Seq) using lungs from mice receiving HIR.We identified 23 different cell types in the lung after HIR and found that this highly complex ecosystem is formed by subpopulations of bone marrow-derived cells that signal to each other and mediate inflammatory responses in different states and at different intervals. Notably, we identified two novel subpopulations with a pro-inflammatory phenotype, EC3, and Neu2, in the HIR group that mediated ALI. We also detected two classes of T cells with distinct cellular functions that mediate more severe ALI through HIR, a CD8+ T cell subpopulation that activates Mon2-CD16 through the CD40LG/CD40 axis and a CD9+ T cell subpopulation that is highly associated with endothelial cells. In addition, we identified possible pathways of action of S100a8 and S100a9 genes in this model.We revealed a cellular landscape of lung tissue after HIR, highlighting the heterogeneity and cellular interactions between major immune cells. These observations provide new insights into the mechanisms of ALI due to HIR and offer new therapeutic strategies to improve post-transplant lung injury.