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ORIGINAL RESEARCH article

Front. Med.
Sec. Nephrology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1434535

Single-cell transcriptome analysis reveals status changes of immune cells in chronic kidney disease

Provisionally accepted
Xinhuan  Fan Xinhuan Fan 1Yuxin  Zhu Yuxin Zhu 2Hao  Kan Hao Kan 2Aiqin  Mao Aiqin Mao 2Changzhu  Li Changzhu Li 2Li  Geng Li Geng 2Ka  Zhang Ka Zhang 2*
  • 1 Lu’an Hospital, Anhui Medical University, Hefei, Anhui Province, China
  • 2 Wuxi Medical College, Jiangnan University, Wuxi, China

The final, formatted version of the article will be published soon.

    Background & Aims: 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.

    Keywords: human kidney, CKD, ScRNA-seq, immune cell, SPP1 macrophages

    Received: 18 May 2024; Accepted: 08 Nov 2024.

    Copyright: © 2024 Fan, Zhu, Kan, Mao, Li, Geng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ka Zhang, Wuxi Medical College, Jiangnan University, Wuxi, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.