Details

Autor(en) / Beteiligte

• 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 F M
• Jonsson, A Helena
• Rangel-Moreno, Javier
• Meednu, Nida
• Rozo, Cristina
• Apruzzese, William
• Eisenhaure, Thomas M
• Lieb, David J
• Boyle, David L
• Mandelin, 2nd, 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

Titel

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

Ist Teil von

• Nature immunology, 2019-07, Vol.20 (7), p.928

Ort / Verlag

United States

Erscheinungsjahr

2019

Link zum Volltext

Beschreibungen/Notizen

• 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, ITGAX TBX21 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 THY1 HLA-DRA fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.