The immune cell landscape in kidneys of patients with lupus nephritis

Nat Immunol. 2019 Jul;20(7):902-914. doi: 10.1038/s41590-019-0398-x. Epub 2019 Jun 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Biopsy
  • Cluster Analysis
  • Computational Biology / methods
  • Epithelial Cells / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Immunophenotyping
  • Interferons / metabolism
  • Kidney / immunology*
  • Kidney / metabolism
  • Kidney / pathology
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Lupus Nephritis / genetics
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / metabolism
  • Lupus Nephritis / pathology
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Molecular Sequence Annotation
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Single-Cell Analysis
  • Transcriptome

Substances

  • Biomarkers
  • Interferons