Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
Research output: Contribution to journal › Article
Colleges, School and Institutes
- Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
- Rheumatology Department, Mile End Hospital, Barts Health NHS Trust, London, UK.
- Department of Pathology & Laboratory Medicine; Weill Cornell Medical College; New York NY USA
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
- Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
- Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
- Arthritis and Tissue Degeneration, Hospital for Special Surgery, New York, NY, USA.
- Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
- Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA.
- Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
- Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY, USA.
- Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY, USA.
- Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
- Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, London, UK.
- Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA
- Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.
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-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) 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 THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.
|Number of pages||15|
|Early online date||6 May 2019|
|Publication status||Published - Jul 2019|