Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
复制标题
DOI：
10.1038/s41590-019-0378-1
复制
发表时间：
2019-07-01
影响因子：
30.5
通讯作者：
Utz, Paul J.
中科院分区：
文献类型：
--
作者：
Zhang, Fan;Wei, Kevin;Utz, Paul J.
为了确定类风湿性关节炎（RA）中驱动关节炎症的细胞群，我们应用单细胞RNA测序（scRNA-seq）、质谱细胞术、批量RNA测序（RNA-seq）和流式细胞术对来自51例RA或骨关节炎（OA）患者滑膜组织样本的T细胞、B细胞、单核细胞和成纤维细胞进行了检测。利用基于5，265个scRNA-seq谱的典型相关分析的综合策略，我们鉴定了18个独特的细胞群体。结合质谱细胞术和转录组学，揭示了RA滑膜中扩增的细胞状态：THY 1（CD 90）（+）HLA-β（hi）亚衬成纤维细胞、IL 1 B（+）促炎单核细胞、ITGAX（+）TBX 21（+）自身免疫相关B细胞和PDCD 1（+）外周辅助T（T-PH）细胞和滤泡辅助T（T-FH）细胞。我们定义了以GZMIK（+）、GZMB（+）和GNLY（+）表型为特征的CD 8（+）T细胞的不同亚群。我们将炎性介质映射到它们的源细胞群;例如，我们将IL 6表达归因于THY 1（+）HLA-III（hi）成纤维细胞，将IL 1B产生归因于促炎性单核细胞。这些人群是RA发病机制的潜在关键介质。
To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to Tcells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)(+)HLA-DRA(hi) sublining fibroblasts, IL1B(+) pro-inflammatory monocytes, ITGAX(+)TBX21(+) autoimmune-associated B cells and PDCD1(+) peripheral helper T (T-PH) cells and follicular helper T (T-FH) cells. We defined distinct subsets of CD8(+)Tcells characterized by GZMIK(+), GZMB(+), and GNLY(+) phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed 1L6 expression to THYl(+)HLA-DRA(hi) fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.