Single-Cell Transcriptomics Indicate That CD163+ Kidney Macrophages Are Pro-Inflammatory and May Orchestrate Further Immune Cell Recruitment to Kidney Lesions in ANCA-Associated Glomerulonephritis
Journal of the American Society of Nephrology, vol. 33, pp. 162
Abstract
Background: Anti-Neutrophil Cytoplasmic Antibodies (ANCA)-associated glomerulonephritis (AGN) affects up to 90% of patients with ANCA-vasculitis and may result in end-stage kidney disease. In AGN kidney biopsies, CD163+ macrophages are abundantly present and linked to disease activity. However, their exact role in the maintenance or resolution of local inflammation remains unclear. Methods: CD163+ kidney macrophages were studied using single-cell RNA sequencing of fresh kidney biopsies of 3 active ANCA patients and one patient receiving a nephrectomy for renal cell carcinoma. Cells were sorted for living (CD45+) immune cells by flowcytometry and whole transcriptome analysis was performed using 10X Genomics’ technology. To aid in the multiomic characterization, 2 samples were incubated with an oligo-antibody cocktail and T and B Cell Receptor Repertoires were sequenced. Results: Over 29,000 cells were sequenced: 2,300 (8%) were identified as CD68+ macrophages. In patient and control samples, 498/19,689 (2.5%) and 320/9,605 (3.3%) cells expressed CD163, respectively. Comparison of gene-expression between CD163+ macrophages of the two groups showed significant upregulation of pro-inflammatory cytokines and chemokines (Log2FoldChange ANCA vs control) (IL1B 1.62, CXCL2 2.25, CXCL3 3.26, CXCL8 2.19, CCL3 1.81, CCL4 2.04), and the complement system (C1Qa 1.79, C1Qb 1.94, C1Qc 1.37, C5aR1 1.43). Expression of CCL17 was downregulated (CCL17 -6.57). Conclusions: CD163+ kidney macrophages are pro-infammatory and may orchestrate further immune cell recruitment to active kidney lesions in AGN. Funding: Private Foundation Support
Authors 8
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands
Amsterdam UMC location University of Amsterdam, Department of Internal Medicine, Section of Nephrology, Amsterdam, Netherlands
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Amsterdam UMC location University of Amsterdam, Department of Epidemiology & Data Science (EDS), Bioinformatics Laboratory, Amsterdam, Netherlands
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands
Amsterdam UMC location University of Amsterdam, Department of Internal Medicine, Section of Nephrology, Amsterdam, Netherlands
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Amsterdam UMC location University of Amsterdam, Department of Epidemiology & Data Science (EDS), Bioinformatics Laboratory, Amsterdam, Netherlands
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Leiden University Medical Center · Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Amsterdam UMC location University of Amsterdam, Department of Pathology, Amsterdam, Netherlands
Leiden University Medical Center, department of Pathology, Leiden, Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam Cardiovascular Sciences
Affiliation as printed
Amsterdam Cardiovascular Sciences, Microcirculation, Amsterdam, Netherlands
Amsterdam UMC location University of Amsterdam, Department of Internal Medicine, Section of Nephrology, Amsterdam, Netherlands
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands
Amsterdam UMC location University of Amsterdam, Department of Internal Medicine, Section of Nephrology, Amsterdam, Netherlands
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands
Amsterdam UMC location University of Amsterdam, Department of Internal Medicine, Section of Nephrology, Amsterdam, Netherlands
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