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

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Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, 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, 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·Nature Immunology
DOI 10.1038/s41590-019-0378-1

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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-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. Defining cell types and their activation status in rheumatoid arthritis (RA) is critical to understanding this disease. Raychaudhuri and colleagues leverage several single-cell -omics approaches to define the cellular processes and pathways in the human RA joint.

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Metadata

Authors
Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Zhang, F., Wei, K., Slowikowski, K., Fonseka, C. Y., Rao, D. A., Kelly, S., Goodman, S. M., Tabechian, D., Hughes, L. B., Salomon-Escoto, K., Watts, G. F. M., Jonsson, A. H., Rangel-Moreno, J., Meednu, N., Rozo, C., Apruzzese, W., Eisenhaure, T. M., Lieb, D. J., Boyle, D. L., Mandelin, A. M., Boyce, B. F., DiCarlo, E., Gravallese, E. M., Gregersen, P. K., Moreland, L., Firestein, G. S., Hacohen, N., Nusbaum, C., Lederer, J. A., Perlman, H., Pitzalis, C., Filer, A., Holers, V. M., Bykerk, V. P., Donlin, L. T., Anolik, J. H., Brenner, M. B., & Raychaudhuri, S.
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2019-05-06
Volume
20
Issue
7
Pages
928-942
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/s41590-019-0378-1
OpenAlex
W2949243209
Cited by
1,367
References
18
FWCI
93.86
Type
journal article
Language
en
Open access
bronze
Licence
www.springer.com/tdm (tdm)

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Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Zhang, F., Wei, K., Slowikowski, K., Fonseka, C. Y., Rao, D. A., Kelly, S., Goodman, S. M., Tabechian, D., Hughes, L. B., Salomon-Escoto, K., Watts, G. F. M., Jonsson, A. H., Rangel-Moreno, J., Meednu, N., Rozo, C., Apruzzese, W., Eisenhaure, T. M., Lieb, D. J., . . . Raychaudhuri, S. (2019). Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nature Immunology. https://doi.org/10.1038/s41590-019-0378-1

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