Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis.

Alivernini, Stefano and MacDonald, Lucy and Elmesmari, Aziza and Finlay, Samuel and Tolusso, Barbara and Gigante, Maria Rita and Petricca, Luca and Di Mario, Clara and Bui, Laura and Perniola, Simone and Attar, Moustafa and Gessi, Marco and Fedele, Anna Laura and Chilaka, Sabarinadh and Somma, Domenico and Sansom, Stephen N and Filer, Andrew and McSharry, Charles and Millar, Neal L and Kirschner, Kristina and Nerviani, Alessandra and Lewis, Myles J and Pitzalis, Costantino and Clark, Andrew R and Ferraccioli, Gianfranco and Udalova, Irina and Buckley, Christopher D and Gremese, Elisa and McInnes, Iain B and Otto, Thomas D and Kurowska-Stolarska, Mariola (2020) Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nature medicine. ISSN 1546-170X.

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Official URL: https://www.nature.com/articles/s41591-020-0939-8

Abstract

Immune-regulatory mechanisms of drug-free remission in rheumatoid arthritis (RA) are unknown. We hypothesized that synovial tissue macrophages (STM), which persist in remission, contribute to joint homeostasis. We used single-cell transcriptomics to profile 32,000 STMs and identified phenotypic changes in patients with early/active RA, treatment-refractory/active RA and RA in sustained remission. Each clinical state was characterized by different frequencies of nine discrete phenotypic clusters within four distinct STM subpopulations with diverse homeostatic, regulatory and inflammatory functions. This cellular atlas, combined with deep-phenotypic, spatial and functional analyses of synovial biopsy fluorescent activated cell sorted STMs, revealed two STM subpopulations (MerTKTREM2 and MerTKLYVE1) with unique remission transcriptomic signatures enriched in negative regulators of inflammation. These STMs were potent producers of inflammation-resolving lipid mediators and induced the repair response of synovial fibroblasts in vitro. A low proportion of MerTK STMs in remission was associated with increased risk of disease flare after treatment cessation. Therapeutic modulation of MerTK STM subpopulations could therefore be a potential treatment strategy for RA.

Item Type: Article
Subjects: WD Diseases and disorders of systemic, metabolic or environmental origin > WD811 Rheumatology
Divisions: Ambulatory Care > Rheumatology
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Depositing User: Mrs Caroline Tranter
Date Deposited: 10 Jul 2020 13:49
Last Modified: 10 Jul 2020 13:49
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3262

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