Nature immunology, 2019-07, Vol.20 (7), p.928-942
- 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, 2nd, 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
- Raychaudhuri, Soumya
2019
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- Autor(en) / Beteiligte
- 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, 2nd, 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
- Raychaudhuri, Soumya
- Titel
- Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
- Ist Teil von
- Nature immunology, 2019-07, Vol.20 (7), p.928-942
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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, ITGAX TBX21 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 THY1 HLA-DRA fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1529-2908eISSN: 1529-2916DOI: 10.1038/s41590-019-0378-1Titel-ID: cdi_pubmed_primary_31061532
- Format
- –
- Schlagworte
- Arthritis, Rheumatoid - genetics, Arthritis, Rheumatoid - metabolism, Arthritis, Rheumatoid - pathology, Autoimmunity - genetics, Biomarkers, Computational Biology - methods, Cross-Sectional Studies, Cytokines - metabolism, Fibroblasts - metabolism, Flow Cytometry, Gene Expression, Gene Expression Profiling - methods, High-Throughput Nucleotide Sequencing, Histocompatibility Antigens Class II - genetics, Histocompatibility Antigens Class II - immunology, Humans, Leukocytes - immunology, Leukocytes - metabolism, Monocytes - immunology, Monocytes - metabolism, Signal Transduction, Single-Cell Analysis - methods, Synovial Membrane - metabolism, Synovial Membrane - pathology, T-Lymphocyte Subsets - immunology, T-Lymphocyte Subsets - metabolism, Transcriptome, Workflow