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

Zhang, Fan and Wei, Kevin and Slowikowski, Kamil and Fonseka, Chamith Y and Rao, Deepak A and Kelly, Stephen and Goodman, Susan M and Tabechian, Darren and Hughes, Laura B and Salomon-Escoto, Karen and Watts, Gerald F M and Jonsson, A Helena and Rangel-Moreno, Javier and Meednu, Nida and Rozo, Cristina and Apruzzese, William and Eisenhaure, Thomas M and Lieb, David J and Boyle, David L and Mandelin, Arthur M and Boyce, Brendan F and DiCarlo, Edward and Gravallese, Ellen M and Gregersen, Peter K and Moreland, Larry and Firestein, Gary S and Hacohen, Nir and Nusbaum, Chad and Lederer, James A and Perlman, Harris and Pitzalis, Costantino and Filer, Andrew and Holers, V Michael and Bykerk, Vivian P and Donlin, Laura T and Anolik, Jennifer H and 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. ISSN 1529-2916. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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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
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QW Microbiology. Immunology
WE Musculoskeletal. Orthopaedics
Divisions: Ambulatory Care > Rheumatology
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Depositing User: Mr Philip O'Reilly
Date Deposited: 15 May 2019 09:40
Last Modified: 15 May 2019 09:40
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/2105

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