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Nat Immunol DOI:10.1038/s41590-019-0378-1

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

Publication TypeJournal Article
Year of Publication2019
AuthorsZhang, F, Wei, K, Slowikowski, K, Fonseka, CY, Rao, DA, Kelly, S, Goodman, SM, Tabechian, D, Hughes, LB, Salomon-Escoto, K, Watts, GFM, A Jonsson, H, Rangel-Moreno, J, Meednu, N, Rozo, C, Apruzzese, W, Eisenhaure, TM, Lieb, DJ, Boyle, DL, Mandelin, AM, Boyce, BF, DiCarlo, E, Gravallese, EM, Gregersen, PK, Moreland, L, Firestein, GS, Hacohen, N, Nusbaum, C, Lederer, JA, Perlman, H, Pitzalis, C, Filer, A, V Holers, M, Bykerk, VP, Donlin, LT, Anolik, JH, Brenner, MB, Raychaudhuri, S
Corporate AuthorsAccelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium
JournalNat Immunol
Date Published2019 May 06

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.


Alternate JournalNat. Immunol.
PubMed ID31061532