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Abstract
Kidney diseases are highly prevalent and treatment is costly. Immune cells play important roles in kidney diseases; however, it has been challenging to investigate the contribution of each cell type in kidney pathophysiology. Recently, the development of single-cell sequencing technology has allowed the extensive study of immune cells in blood, secondary lymphoid tissues, kidney biopsy and urine samples, helping researchers generate a comprehensive immune cell atlas for various kidney diseases. Here, we discuss several recent studies using scRNA-seq technology to explore the immune-related kidney diseases, including lupus nephritis, diabetic kidney disease, IgA nephropathy, and anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. Application of scRNA-seq successfully defined the transcriptome profiles of resident and infiltrating immune cells, as well as the intracellular communication networks between immune and adjacent cells. In addition, the discovery of similar immune cells in blood and urine suggests the possibility of examining kidney immunity without biopsy. In conclusion, these immune cell atlases will increase our understanding of kidney immunology and contribute to novel therapeutics for patients with kidney diseases.
Highlights
The kidneys are vital organs serving critical functions in the human body, including clearance of waste from blood, maintenance of the salt/water balance, and regulation of blood pressure
This study demonstrated a correlation between type I interferon signaling in renal tubular cells and skin keratinocytes in patients with active lupus nephritis, suggesting the potential of evaluating Lupus nephritis (LN) activity with skin biopsy samples
With scRNA-seq, no B cells were found in healthy kidneys, which was confirmed by the flow cytometry assay. These results identify the cell populations that contribute to immunemediated kidney injury in lupus nephritis and provide novel insights into B cells and plasma cells, showing that they may contribute to LN pathogenesis through clonal expansion at the site of injury; further studies are needed to investigate the detailed mechanism
Summary
The kidneys are vital organs serving critical functions in the human body, including clearance of waste from blood, maintenance of the salt/water balance, and regulation of blood pressure. We discuss recent findings focusing on several immune-related kidney diseases, including LN, DKD, IgAN, and ANCA-GN, highlighting the changes in immune cell populations and the possible immune mechanisms revealed by scRNA-seq technology. Single-cell preparation is the first step of all scRNA-seq technologies which require fresh tissue samples and successful dissociation of tissue to generate good quality data and cells should be smaller than the droplets or microwells. To overcome these technical barriers, researchers developed the single-nucleus RNA-sequencing (snRNA-seq) method (Krishnaswami et al, 2016; Lacar et al, 2016; Habib et al, 2017), where nuclear, not cytoplasmic RNA is sequenced. Arazi et al, 2019 Der et al, 2019 Fu et al, 2019 Wilson et al, 2019 Zheng et al, 2020 Tang et al, 2021 Krebs et al, 2020
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