Author:
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.,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,Buyon Jill P.,Petri Michelle A.,Putterman Chaim,Kalunian Kenneth C.,Woodle E. Steve,Lederer James A.,Hildeman David A.,Nusbaum Chad,Wofsy David,Kretzler Matthias,Anolik Jennifer H.,Brenner Michael B.,Hacohen Nir,Diamond Betty,
Abstract
ABSTRACTLupus nephritis is a potentially fatal autoimmune disease, whose current treatment is ineffective and often toxic. To gain insights into disease mechanisms, we analyzed kidney samples from lupus nephritis patients and healthy controls using single-cell RNA-seq. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid, T, NK and B cells, demonstrating both pro-inflammatory and resolving responses. We found evidence of local activation of B cells correlated with an age-associated B cell signature, and 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, pointing to potential therapeutic targets. Gene expression of immune cells in urine and kidney was highly correlated, suggesting urine may be a surrogate for kidney biopsies. Our results provide a first comprehensive view of the complex network of leukocytes active in lupus nephritis kidneys.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献