The immune cell landscape in kidneys of patients with lupus nephritis

• Published in: Nature immunology Vol. 20; no. 7; pp. 902 - 914
• Main Authors: Arazi, Arnon, Rao, Deepak A., Berthier, Celine C., Davidson, Anne, Liu, Yanyan, Hoover, Paul J., Chicoine, Adam, Eisenhaure, Thomas M., Jonsson, A. Helena, Li, Shuqiang, Lieb, David J., Zhang, Fan, Slowikowski, Kamil, Browne, Edward P., Noma, Akiko, Sutherby, Danielle, Steelman, Scott, Smilek, Dawn E., Tosta, Patti, Apruzzese, William, Massarotti, Elena, Dall’Era, Maria, Park, Meyeon, Kamen, Diane L., Furie, Richard A., Payan-Schober, Fernanda, Pendergraft, William F., McInnis, Elizabeth A., Buyon, Jill P., Petri, Michelle A., Putterman, Chaim, Kalunian, Kenneth C., Woodle, E. Steve, Lederer, James A., Hildeman, David A., Nusbaum, Chad, Raychaudhuri, Soumya, Kretzler, Matthias, Anolik, Jennifer H., Brenner, Michael B., Wofsy, David, Hacohen, Nir, Diamond, Betty
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2019; Nature Publishing Group
• Subjects: 631/1647/514/1949; 631/250/256; 631/250/38; 692/699/249/1313; Age; Analysis; Autoimmune diseases; Biomarkers; Biomedical and Life Sciences; Biomedicine; Biopsy; Care and treatment; Cell activation; Chemokine receptors; Cluster Analysis; Complications and side effects; Computational Biology - methods; CX3CR1 protein; CXCR4 protein; Epithelial Cells - metabolism; Flow Cytometry; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Health aspects; Humans; Immunohistochemistry; Immunology; Immunophenotyping; Infectious Diseases; Inflammation; Interferon; Interferons - metabolism; Kidney - immunology; Kidney - metabolism; Kidney - pathology; Kidneys; Leukocytes; Leukocytes - immunology; Leukocytes - metabolism; Lupus; Lupus nephritis; Lupus Nephritis - genetics; Lupus Nephritis - immunology; Lupus Nephritis - metabolism; Lupus Nephritis - pathology; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphocytes B; Lymphocytes T; Molecular Sequence Annotation; Monocytes; Myeloid cells; Myeloid Cells - immunology; Myeloid Cells - metabolism; Natural killer cells; Nephritis; Resource; Ribonucleic acid; Risk factors; RNA; Single-Cell Analysis; Systemic lupus erythematosus; Transcription; Transcriptome; Urine
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-019-0398-x

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1 , were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies. Much about the kidney-resident immune populations is a black box. Hacohen and colleagues use single cell RNA sequencing of kidney, skin and urine from lupus nephritis patients to describe the transcriptional state of the immune cells present in each compartment.