Ischemia-reperfusion is an unavoidable step of organ transplantation. Development of therapeutics for lung injury during transplantation has proved challenging; understanding lung injury from human data at the single-cell resolution is required to accelerate the development of therapeutics. Donor lung biopsies from 6 human lung transplant cases were collected at the end of cold preservation and 2-hour reperfusion and underwent single-cell RNA sequencing. Donor and recipient origin of cells from the reperfusion timepoint were deconvolved. Gene expression profiles were: (1) compared between each donor cell type between timepoints and (2) compared between donor and recipient cells. Inflammatory responses from donor lung macrophages were found after reperfusion with upregulation of multiple cytokines and chemokines, especially IL-1β and IL-1α. Significant inflammatory responses were found in alveolar epithelial cells (featured by CXCL8) and lung endothelial cells (featured by IL-6 upregulation). Different inflammatory responses were noted between donor and recipient monocytes and CD8+ T cells. The inflammatory signals and differences between donor and recipient cells observed provide insight into the cellular and molecular mechanisms of ischemia-reperfusion induced lung injury. Further investigations may lead to the development of novel targeted therapeutics.

中文翻译：

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单细胞分辨率下人肺移植的缺血再灌注反应


缺血再灌注是器官移植不可避免的步骤。事实证明，开发移植期间肺损伤的治疗方法具有挑战性;需要从单细胞分辨率的人类数据中了解肺损伤，以加速治疗药物的开发。在冷保存和 2 小时再灌注结束时收集 6 例人肺移植病例的供体肺活检，并进行单细胞 RNA 测序。对再灌注时间点细胞的供体和受体来源进行反卷积。基因表达谱是：（1） 在时间点之间比较每种供体细胞类型，以及 （2） 在供体细胞和受体细胞之间进行比较。在再灌注多种细胞因子和趋化因子（尤其是 IL-1β 和 IL-1α）上调后发现供体肺巨噬细胞的炎症反应。在肺泡上皮细胞 （以 CXCL8 为特征） 和肺内皮细胞 （以 IL-6 上调为特征） 中发现显着的炎症反应。供体和受体单核细胞以及 CD8+ T 细胞之间的炎症反应不同。观察到的炎症信号以及供体细胞和受体细胞之间的差异有助于深入了解缺血再灌注诱导的肺损伤的细胞和分子机制。进一步的研究可能会导致新型靶向治疗药物的开发。