Welcome
Here, you can explore our single-cell RNA sequencing data to investigate the phenotypic spectrum of synovial tissue macrophage during development and resolution of rheumatoid arthritis (RA). Analyses were performed using the Seurat pipeline and custom scripts which are available upon request. In this web application we use a random subset of 8000 cells for faster computation. Further details can be found in our paper summarized below which you should cite if you use our data.
Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis
Stefano Alivernini, Lucy MacDonald, Aziza Elmesmari, Samuel Finlay, Barbara Tolusso, Maria Rita Gigante, Luca Petricca, Clara Di Mario, Laura Bui, Simone Perniola, Moustafa Attar, Marco Gessi, Anna Laura Fedele, Sabarinadh Chilaka, Domenico Somma, Stephen Sansom, Andrew Filer, Charles McSharry, Neal L. Millar, Kristina Kirschner, Alessandra Nerviani, Myles J. Lewis, Costantino Pitzalis, Andrew R. Clark, Gianfranco Ferraccioli, Irina Udalova, Christopher D. Buckley, Elisa Gremese, Iain B. McInnes, Thomas D. Otto and Mariola Kurowska-Stolarska
Abstract
Immune-regulatory mechanisms of drug-free remission in rheumatoid arthritis (RA) are unknown. We hypothesised that synovial tissue macrophages (STM), which persist in remission, contribute to joint homeostasis. We used single-cell transcriptomics to profile 32000 STMs and identified phenotypic changes in patients with early/active RA, treatment-refractory/active RA and RA in sustained remission. Each clinical state was characterised by different frequencies of 9 discrete phenotypic clusters within 4 distinct STM subpopulations with diverse homeostatic, regulatory and inflammatory functions. This cellular atlas combined with deep-phenotypic, spatial and functional analyses of synovial biopsy FACS-sorted STMs revealed two STM subpopulations (MerTKpos/TREM2high and MerTKpos/LYVE1pos) 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 MerTKpos STMs in remission was predictive of flare after treatment cessation. Therapeutic fostering of MerTKpos STM-subpopulations could therefore be a successful strategy for RA treatment.
- Clustering - Allows cluster visualization and exploration of top cluster markers.
- Differential expression (DE) - Comparison of gene expression in macrophages from healthy, UPA, Naive RA, Resistant RA and Remission RA using parameters specified in our paper (i.e the first 12 Principal components and 0.5 as the clustering resolution).
