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

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, 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 and Raychaudhuri, Soumya (2019) Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nature immunology, 20 (7). pp. 928-942. ISSN 1529-2916.

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Official URL: https://www.nature.com/articles/s41590-019-0378-1

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-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.

Item Type: Article
Subjects: QW Microbiology. Immunology
WD Diseases and disorders of systemic, metabolic or environmental origin > WD811 Rheumatology
Divisions: Ambulatory Care > Rheumatology
Related URLs:
Depositing User: Beth Connors
Date Deposited: 15 Jul 2019 12:06
Last Modified: 15 Jul 2019 12:06
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2230

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