1. Publications

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

Fan Zhang#, Kevin Wei#, Kamil Slowikowski#, Chamith Y Fonseka#, Deepak A Rao#, Stephen Kelly, Susan M Goodman, Darren Tabechian, Laura B Hughes, Karen Salomon-Escoto, Gerald F M Watts, A Helena Jonsson, Javier Rangel-Moreno, Nida Meednu, Cristina Rozo, William Apruzzese, Thomas M Eisenhaure, David J Lieb, David L Boyle, Arthur M Mandelin 2nd; Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium; Brendan F Boyce, Edward DiCarlo, Ellen M Gravallese, Peter K Gregersen, Larry Moreland, Gary S Firestein, Nir Hacohen, Chad Nusbaum, James A Lederer, Harris Perlman, Costantino Pitzalis, Andrew Filer, V Michael Holers, Vivian P Bykerk, Laura T Donlin, Jennifer H Anolik, Michael B Brenner, Soumya Raychaudhuri.
Nat Immunol. 2019-05-06;20(7):928-942.
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.

Related data

Data summary
The single-cell RNA-seq data, bulk RNA-seq data, mass cytometry data, flow cytometry data, and the clinical and histological data for this study are available at ImmPort (study accession code SDY998).
Data summary
The raw single-cell RNA-seq data are deposited in dbGaP.
Data summary
The source code repository of the computational and statistical analysis is located at https://github.com/immunogenomics/amp_phase1_ra.
Data summary
Data can also be viewed on three different websites 1/3.
Data summary
Data can also be viewed on three different websites 2/3.
Data summary
Data can also be viewed on three different websites 3/3.