Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Division of Rheumatology, Immunology, Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Immunol. 2019 Jul;20(7):902-914. doi: 10.1038/s41590-019-0398-x. Epub 2019 Jun 17.
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.
狼疮性肾炎是一种潜在致命的自身免疫性疾病，目前的治疗方法无效且往往有毒。为了研究疾病的发病机制，我们使用单细胞 RNA 测序分析了狼疮性肾炎患者和健康对照者的肾脏样本。我们的分析揭示了 21 种白细胞亚群在疾病中活跃，包括多种髓样细胞、T 细胞、自然杀伤细胞和 B 细胞，这些细胞表现出促炎反应和炎症缓解反应。我们发现了与年龄相关的 B 细胞特征相关的局部 B 细胞激活的证据，以及肾脏内单核细胞分化的进展阶段的证据。在大多数细胞中观察到明显的干扰素反应。两种趋化因子受体 CXCR4 和 CX3CR1 广泛表达，暗示其在细胞迁移中可能具有核心作用。尿液和肾脏中免疫细胞的基因表达高度相关，这表明尿液可能可作为肾活检的替代物。
