通过整合单细胞转录组学和液质联用技术定义类风湿关节炎关节滑膜组织中的炎症细胞状态。

Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry.

机构信息

Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.

Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

出版信息

Nat Immunol. 2019 Jul;20(7):928-942. doi: 10.1038/s41590-019-0378-1. Epub 2019 May 6.

DOI:10.1038/s41590-019-0378-1

PMID:31061532

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6602051/

Abstract

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 T cells, 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 sublining fibroblasts, IL1B pro-inflammatory monocytes, ITGAXTBX21 autoimmune-associated B cells and PDCD1 peripheral helper T (T) cells and follicular helper T (T) cells. We defined distinct subsets of CD8 T cells characterized by GZMK, GZMB, and GNLY phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1HLA-DRA fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

摘要

为了明确类风湿关节炎（RA）关节炎症的驱动细胞群体，我们应用单细胞 RNA 测序（scRNA-seq）、液质联用流式细胞术、批量 RNA 测序（RNA-seq）和流式细胞术，对 51 例 RA 或骨关节炎（OA）患者的滑膜组织中的 T 细胞、B 细胞、单核细胞和成纤维细胞进行了研究。利用基于 5265 个 scRNA-seq 图谱的典型相关分析的综合策略，我们鉴定出 18 个独特的细胞群体。结合液质联用流式细胞术和转录组学揭示了 RA 滑膜中扩增的细胞状态：THY1（CD90）HLA-DRA 下皮成纤维细胞、IL1B 促炎单核细胞、ITGAXTBX21 自身免疫相关 B 细胞和 PDCD1 外周辅助性 T（T）细胞及滤泡辅助性 T（T）细胞。我们定义了具有 GZMK、GZMB 和 GNLY 表型的不同 CD8 T 细胞亚群。我们将炎症介质映射到其来源的细胞群体；例如，我们将 IL6 表达归因于 THY1HLA-DRA 成纤维细胞，将 IL1B 产生归因于促炎单核细胞。这些群体可能是 RA 发病机制的关键介质。