The immune cell landscape in kidneys of patients with lupus nephritis.
Biomarkers
Biopsy
Cluster Analysis
Computational Biology
/ methods
Epithelial Cells
/ metabolism
Flow Cytometry
Gene Expression Profiling
Gene Expression Regulation
Humans
Immunophenotyping
Interferons
/ metabolism
Kidney
/ immunology
Leukocytes
/ immunology
Lupus Nephritis
/ genetics
Lymphocytes
/ immunology
Molecular Sequence Annotation
Myeloid Cells
/ immunology
Single-Cell Analysis
Transcriptome
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
18
04
2018
accepted:
05
04
2019
pubmed:
19
6
2019
medline:
10
7
2019
entrez:
19
6
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31209404
doi: 10.1038/s41590-019-0398-x
pii: 10.1038/s41590-019-0398-x
pmc: PMC6726437
mid: NIHMS1526529
doi:
Substances chimiques
Biomarkers
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
902-914Subventions
Organisme : NIAMS NIH HHS
ID : UH2 AR067685
Pays : United States
Organisme : NIAMS NIH HHS
ID : UM2 AR067678
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067681
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067688
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067689
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067690
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067694
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK081943
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067679
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009379
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067677
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067676
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067691
Pays : United States
Investigateurs
Arnon Arazi
(A)
Deepak A Rao
(DA)
Celine C Berthier
(CC)
Anne Davidson
(A)
Yanyan Liu
(Y)
Paul J Hoover
(PJ)
Adam Chicoine
(A)
Thomas M Eisenhaure
(TM)
A Helena Jonsson
(AH)
Shuqiang Li
(S)
David J Lieb
(DJ)
Fan Zhang
(F)
Kamil Slowikowski
(K)
Edward P Browne
(EP)
Akiko Noma
(A)
Danielle Sutherby
(D)
Scott Steelman
(S)
Dawn E Smilek
(DE)
Patti Tosta
(P)
William Apruzzese
(W)
Elena Massarotti
(E)
Maria Dall'Era
(M)
Meyeon Park
(M)
Diane L Kamen
(DL)
Richard A Furie
(RA)
Fernanda Payan-Schober
(F)
William F Pendergraft
(WF)
Elizabeth A McInnis
(EA)
Jill P Buyon
(JP)
Michelle A Petri
(MA)
Chaim Putterman
(C)
Kenneth C Kalunian
(KC)
E Steve Woodle
(ES)
James A Lederer
(JA)
David A Hildeman
(DA)
Chad Nusbaum
(C)
Soumya Raychaudhuri
(S)
Matthias Kretzler
(M)
Jennifer H Anolik
(JH)
Michael B Brenner
(MB)
David Wofsy
(D)
Nir Hacohen
(N)
Betty Diamond
(B)
Dia Waguespack
(D)
Sean M Connery
(SM)
Maureen A McMahon
(MA)
William J McCune
(WJ)
Ruba B Kado
(RB)
Raymond Hsu
(R)
Melissa A Cunningham
(MA)
Paul J Utz
(PJ)
Mina Pichavant
(M)
Holden T Maecker
(HT)
Rohit Gupta
(R)
Judith A James
(JA)
Joel M Guthridge
(JM)
Chamith Fonseka
(C)
Evan Der
(E)
Robert Clancy
(R)
Thomas Tuschl
(T)
Hemant Suryawanshi
(H)
Andrea Fava
(A)
H Michael Belmont
(HM)
Peter M Izmirly
(PM)
Pavel Morozov
(P)
Manjunath Kustagi
(M)
Daniel H Goldman
(DH)
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
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