The immune cell landscape in kidneys of patients with lupus nephritis

Abstract

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.

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Affiliated Institutions

• Brigham and Women's Hospital US
• Texas Tech University US
• University of Rochester Medical Center US
• Harvard University US
• Celsius Therapeutics (United States) US
• University of Cincinnati US
• Feinstein Institute for Medical Research US
• Immune Tolerance Network US
• Texas Tech University Health Sciences Center US
• University of California, San Diego US
• Cincinnati Children's Hospital Medical Center US
• University of Michigan US
• Montefiore Medical Center US
• Albert Einstein College of Medicine US
• New York University US
• Johns Hopkins University US
• Northwell Health US
• Broad Institute US
• University of California, San Francisco US
• University of North Carolina at Chapel Hill US
• Medical University of South Carolina US
• University of Cincinnati Medical Center US

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