Cell type–specific inflammatory response of ischemia-reperfusion injury in lung transplantation

Lung transplantation is a lifesaving therapy for patients with end-stage lung disease. Ischemia-reperfusion injury (IRI), however, contributes to the development of primary graft dysfunction and poor clinical outcomes. Inflammation is a major mechanism of IRI, characterized by alveolar macrophage activation and recruitment of leukocytes (neutrophils, monocytes, and lymphocytes) into lung grafts. Beyond their role as injury targets, pulmonary epithelial and endothelial cells actively regulate inflammatory response and cell death. Activation of immunosuppressive cells for the resolution of inflammation is crucial to promote allograft recovery from IRI. Preclinical studies using transgenic mice, cell culture, and small and large animal lung transplantation models have revealed potential molecular mechanisms and therapeutic targets. Transcriptomics, metabolomics, and single-cell RNA sequencing have provided opportunities to explore dynamic gene expression and metabolic shifts during IRI. In this review, we reviewed current knowledge of IRI in a cell type–specific manner, focusing on the translation of basic discoveries into clinical applications to improve outcomes in lung transplantation.