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

The immune cell landscape in kidneys of patients with lupus nephritis.

Author information

1
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
2
Division of Rheumatology, Immunology, Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
3
Internal Medicine, Department of Nephrology, University of Michigan, Ann Arbor, MI, USA.
4
Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA.
5
UNC HIV Cure Center and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
6
Celsius Therapeutics, Cambridge, MA, USA.
7
Cellarity, Inc., Cambridge, MA, USA.
8
Lupus Nephritis Trials Network, University of California San Francisco, San Francisco, CA, USA.
9
Immune Tolerance Network, University of California San Francisco, San Francisco, CA, USA.
10
Rheumatology Division, University of California San Francisco, San Francisco, CA, USA.
11
Division of Nephrology, University of California San Francisco, San Francisco, CA, USA.
12
Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
13
Division of Rheumatology, Northwell Health, Great Neck, NY, USA.
14
Department of Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
15
The Integrative Medical Clinic of North Carolina, PLLC, Chapel Hill, NC, USA.
16
University of North Carolina Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, UNC School of Medicine, Chapel Hill, NC, USA.
17
Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY, USA.
18
Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USA.
19
Division of Rheumatology and Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
20
University of California San Diego School of Medicine, La Jolla, CA, USA.
21
Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
22
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
23
Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA.
24
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
25
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA.
26
Broad Institute of MIT and Harvard, Cambridge, MA, USA. nhacohen@mgh.harvard.edu.
27
Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA. BDiamond@northwell.edu.

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.

PMID:
31209404
DOI:
10.1038/s41590-019-0398-x
[Indexed for MEDLINE]

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