TY - JOUR
T1 - Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
AU - Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium
AU - Zhang, Fan
AU - Wei, Kevin
AU - Slowikowski, Kamil
AU - Fonseka, Chamith Y
AU - Rao, Deepak A
AU - Kelly, Stephen
AU - Goodman, Susan M
AU - Tabechian, Darren
AU - Hughes, Laura B
AU - Salomon-Escoto, Karen
AU - Watts, Gerald F M
AU - Jonsson, A Helena
AU - Rangel-Moreno, Javier
AU - Meednu, Nida
AU - Rozo, Cristina
AU - Apruzzese, William
AU - Eisenhaure, Thomas M
AU - Lieb, David J
AU - Boyle, David L
AU - Mandelin, Arthur M
AU - Turner, Jason
AU - Boyce, Brendan F
AU - DiCarlo, Edward
AU - Gravallese, Ellen M
AU - Gregersen, Peter K
AU - Moreland, Larry
AU - Firestein, Gary S
AU - Hacohen, Nir
AU - Nusbaum, Chad
AU - Lederer, James A
AU - Perlman, Harris
AU - Pitzalis, Costantino
AU - Filer, Andrew
AU - Holers, V Michael
AU - Bykerk, Vivian P
AU - Donlin, Laura T
AU - Anolik, Jennifer H
AU - Brenner, Michael B
AU - Raychaudhuri, Soumya
AU - Buckley, Christopher
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85065310005&partnerID=8YFLogxK
U2 - 10.1038/s41590-019-0378-1
DO - 10.1038/s41590-019-0378-1
M3 - Article
C2 - 31061532
SN - 1529-2908
VL - 20
SP - 928
EP - 942
JO - Nature Immunology
JF - Nature Immunology
IS - 7
ER -