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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1405748
This article is part of the Research Topic Deciphering the Intricate Relationship between Epigenetics and Transcription in Immune System Regulation View all 6 articles

Integrated temporal transcriptional and epigenetic single-cell analysis reveals the intrarenal immune characteristics in an early-stage model of IgA nephropathy during its acute injury

Provisionally accepted
Chen Xu Chen Xu 1Yiwei Zhang Yiwei Zhang 1*Jian Zhou Jian Zhou 1*Jiangnan Zhang Jiangnan Zhang 2*Hui Dong Hui Dong 1*Xiangmei Chen Xiangmei Chen 3Yi Tian Yi Tian 1Yuzhang Wu Yuzhang Wu 1*
  • 1 Institute of Immunology, Third Military Medical University, Chongqing, China
  • 2 Second Affiliated Hospital, Third Military Medical University, Chongqing, China
  • 3 Department of Nephrology, Chinese PLA General Hospital, Beijing, Beijing Municipality, China

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

    Rationale: Kidney inflammation plays a crucial role in the pathogenesis of IgA nephropathy (IgAN), yet the specific phenotypes of immune cells involved in disease progression remain incompletely understood. Utilizing joint profiling through longitudinal single-cell RNA-sequencing (scRNAseq) and single-cell assay for transposase-accessible chromatin sequencing (scATACseq) can provide a comprehensive framework for elucidating the development of cell subset diversity and how chromatin accessibility regulates transcription.Objective: We aimed to characterize the dynamic immune cellular landscape at a high resolution in an early IgAN mouse model with acute kidney injury (AKI).A murine model was utilized to mimic 3 immunological states-"immune stability (IS), immune activation (IA) and immune remission (IR)" in early human IgAN-associated glomerulopathy during AKI, achieved through lipopolysaccharide (LPS) injection. Urinary albumin to creatinine ratio (UACR) was measured to further validate the exacerbation and resolution of kidney inflammation during this course. Paired scRNAseq and scATACseq analysis was performed on CD45+ immune cells isolated from kidney tissues obtained from CTRL (healthy vehicle), IS, IA and IR (4 or 5 mice each). Our data offer an impartial depiction of the immunological characteristics, as the proportions of immune cell types fluctuated throughout different stages of the disease. Specifically, these analyses also revealed novel subpopulations, such as a macrophage subset (Nlrp1b Mac) with distinct epigenetic features and a unique transcription factor motif profile, potentially exerting immunoregulatory effects, as well as an early subset of Tex distinguished by their effector and cytolytic potential (CX3CR1-transTeff). Furthermore, in order to investigate the potential interaction between immune cells and renal resident cells, we conducted single-cell RNA sequencing on kidney cells obtained from a separate cohort of IS and IA mice without isolating immune cells. These findings underscored the diverse roles played by macrophages and CD8+ T cells in maintaining homeostasis of endothelial cells (ECs) under stress.Conclusions: This study presents a comprehensive analysis of the dynamic changes in immune cell profiles in a model of IgAN, identifying key cell types and their roles and interactions. These findings significantly contribute to the understanding of the pathogenesis of IgAN and may provide potential targets for therapeutic intervention.

    Keywords: IgA nephropathy, immune cells, single-cell RNA-seq, Single-cell ATAC-seq, Macrophages, CD8 + T cells

    Received: 23 Mar 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Xu, Zhang, Zhou, Zhang, Dong, Chen, Tian and Wu. 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:
    Yiwei Zhang, Institute of Immunology, Third Military Medical University, Chongqing, China
    Jian Zhou, Institute of Immunology, Third Military Medical University, Chongqing, China
    Jiangnan Zhang, Second Affiliated Hospital, Third Military Medical University, Chongqing, China
    Hui Dong, Institute of Immunology, Third Military Medical University, Chongqing, China
    Yuzhang Wu, Institute of Immunology, Third Military Medical University, Chongqing, 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.