학술논문
Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
Document Type
article
Author
Zhang, Fan; Wei, Kevin; Slowikowski, Kamil; Fonseka, Chamith Y; Rao, Deepak A; Kelly, Stephen; Goodman, Susan M; Tabechian, Darren; Hughes, Laura B; Salomon-Escoto, Karen; Watts, Gerald FM; Jonsson, A Helena; Rangel-Moreno, Javier; Meednu, Nida; Rozo, Cristina; Apruzzese, William; Eisenhaure, Thomas M; Lieb, David J; Boyle, David L; Mandelin, Arthur M; Boyce, Brendan F; DiCarlo, Edward; Gravallese, Ellen M; Gregersen, Peter K; Moreland, Larry; Firestein, Gary S; Hacohen, Nir; Nusbaum, Chad; Lederer, James A; Perlman, Harris; Pitzalis, Costantino; Filer, Andrew; Holers, V Michael; Bykerk, Vivian P; Donlin, Laura T; Anolik, Jennifer H; Brenner, Michael B; Raychaudhuri, Soumya
Source
Nature Immunology. 20(7)
Subject
Language
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-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) 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 THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.