Contrary to immune cells, the response of the kidney structural cells in rejection is less established. We performed single-cell RNA sequencing of 18 kidney transplant biopsies from 14 recipients. Single-cell RNA sequencing identified cells from the major compartments of the kidney, next to infiltrated immune cells. Endothelial cells from the glomerulus, peritubular capillaries, and vasa recta showed upregulation of class I and II human leukocyte antigen genes, adhesion molecules, cytokines, and chemokines, suggesting active participation in the alloimmune process, with compartment-specific differences. Epithelial cells including proximal tubular, loop of Henle, and collecting duct cells, also showed increased expression of immune genes. Strikingly, in proximal tubule cells, a strong downregulation of energy metabolism upon inflammation was observed. There was a large overlap between the cell-specific expression changes upon alloimmune inflammation and those observed in 2 large microarray biopsy cohorts. In conclusion, the kidney structural cells, being the main target of the alloimmune process, appear to actively contribute herein, enhancing the damaging effects of the infiltrating immune cells. In epithelial cells, a profound shutdown of metabolism was seen upon inflammation, which is associated with poor kidney function. These observations highlight the critical role of the graft in triggering and sustaining rejection after transplantation.

中文翻译：

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肾移植排斥反应期间肾结构细胞的积极免疫参与和代谢关闭


与免疫细胞相反，肾脏结构细胞对排斥反应的反应不太确定。我们对 14 名受者的 18 例肾移植活检进行了单细胞 RNA 测序。单细胞 RNA 测序鉴定了来自肾脏主要隔室的细胞，旁边是浸润的免疫细胞。来自肾小球、肾小管周围毛细血管和直肠血管的内皮细胞显示 I 类和 II 类人类白细胞抗原基因、粘附分子、细胞因子和趋化因子的上调，表明积极参与同种免疫过程，但存在区室特异性差异。上皮细胞，包括近端肾小管、Henle 环和集合管细胞，也显示免疫基因表达增加。引人注目的是，在近端小管细胞中，观察到炎症后能量代谢的强烈下调。同种免疫炎症后的细胞特异性表达变化与在 2 个大型微阵列活检队列中观察到的变化之间存在很大重叠。总之，肾脏结构细胞作为同种免疫过程的主要靶标，似乎在此积极贡献，增强了浸润免疫细胞的破坏作用。在上皮细胞中，炎症后观察到新陈代谢的严重关闭，这与肾功能不佳有关。这些观察结果强调了移植物在移植后触发和维持排斥反应中的关键作用。