Fan Xinhuan, Zhu Yuxin, Kan Hao, Mao Aiqin, Geng Li, Li Changzhu, Zhang Ka
Department of Urology, Lu'an Hospital of Anhui Medical University, Lu'an, China.
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Front Med (Lausanne). 2024 Dec 3;11:1434535. doi: 10.3389/fmed.2024.1434535. eCollection 2024.
The immune system plays a crucial role in the development of kidney diseases. Chronic kidney disease (CKD) can lead to various complications, potentially affecting multiple systems throughout the body. Currently, the description of the immune system in human CKD is not comprehensive enough. Constructing a CKD kidney atlas using single-cell RNA sequencing (scRNA-seq) can provide deeper insights into the composition and functional changes of immune cells in CKD, facilitating the discovery of new therapeutic targets.
We processed and integrated scRNA-seq datasets from healthy and CKD kidneys from three independent cohorts using the same approach (including 42 normal samples and 23 chronic kidney disease samples). Subsequently, we conducted gene enrichment and intercellular communication analysis to construct an immune cell atlas of the kidneys in CKD patients.
We identified nine major kidney cell clusters. Further clustering analysis of different immune cell clusters revealed that, compared to normal kidneys, CKD patients' kidneys had decreased CD16+ NK cells while CD4+ naive helper T cells and CCR7+ DC increased. Partial activation of the WNT signaling pathway was observed in T cells and NK cells of CKD patients, while some metabolism-related genes were inhibited. Myeloid cell subgroups also exhibited abnormal signaling pathway alterations. Additionally, we discovered a unique population of SPP1 macrophages in CKD, which are recruited by chemokines released from aPT and aTAL cell subpopulations. These SPP1 macrophages may promote cellular fibrosis through the signaling of SPP1, FN1, and various receptors.
We established a human CKD kidney immune cell atlas and identified SPP1 macrophages as a unique cell type in CKD. The interaction between SPP1 macrophages and damaged cells may serve as a potential therapeutic target for treating CKD in the future.
免疫系统在肾脏疾病的发展中起着至关重要的作用。慢性肾脏病（CKD）可导致各种并发症，可能影响全身多个系统。目前，对人类CKD中免疫系统的描述还不够全面。使用单细胞RNA测序（scRNA-seq）构建CKD肾脏图谱可以更深入地了解CKD中免疫细胞的组成和功能变化，有助于发现新的治疗靶点。
我们使用相同的方法（包括42个正常样本和23个慢性肾脏病样本）处理并整合了来自三个独立队列的健康和CKD肾脏的scRNA-seq数据集。随后，我们进行了基因富集和细胞间通讯分析，以构建CKD患者肾脏的免疫细胞图谱。
我们鉴定出九个主要的肾脏细胞簇。对不同免疫细胞簇的进一步聚类分析表明，与正常肾脏相比，CKD患者的肾脏中CD16+自然杀伤细胞减少，而CD4+初始辅助性T细胞和CCR7+树突状细胞增加。在CKD患者的T细胞和自然杀伤细胞中观察到WNT信号通路的部分激活，而一些与代谢相关的基因受到抑制。髓样细胞亚群也表现出异常的信号通路改变。此外，我们在CKD中发现了一种独特的SPP1巨噬细胞群体，它们由aPT和aTAL细胞亚群释放的趋化因子招募。这些SPP1巨噬细胞可能通过SPP1、FN1和各种受体的信号传导促进细胞纤维化。
我们建立了人类CKD肾脏免疫细胞图谱，并将SPP1巨噬细胞鉴定为CKD中一种独特的细胞类型。SPP1巨噬细胞与受损细胞之间的相互作用可能成为未来治疗CKD的潜在治疗靶点。
