The immune cell landscape in kidneys of patients with lupus nephritis
The immune cell landscape in kidneys of patients with lupus nephritis
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DOI：
10.1038/s41590-019-0398-x
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发表时间：
2019-07-01
影响因子：
30.5
通讯作者：
Goldman, Daniel H.
中科院分区：
文献类型：
--
作者：
Arazi, Arnon;Rao, Deepak A.;Goldman, Daniel H.
狼疮性肾炎是一种潜在的致命的自身免疫性疾病，目前的治疗是无效的，往往有毒。为了发展疾病的机制假说，我们使用单细胞RNA测序分析了狼疮肾炎患者和健康对照受试者的肾脏样本。我们的分析揭示了21个在疾病中活跃的白细胞亚群，包括髓样细胞、T细胞、自然杀伤细胞和B细胞的多个群体，这些细胞表现出促炎反应和炎症消退反应。我们发现B细胞局部活化的证据与年龄相关的B细胞特征和肾脏内单核细胞分化的进展阶段的证据相关。在大多数细胞中观察到明显的干扰素应答。两种趋化因子受体，CXCR4和CX3CR1，广泛表达，这意味着在细胞运输中的潜在核心作用。尿液和肾脏中免疫细胞的基因表达高度相关，这表明尿液可能作为肾脏活检的替代物。
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, Tcells, 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.