دورية أكاديمية
Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
| العنوان: | Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry |
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| المؤلفون: | Zhang, F, Wei, K, Slowikowski, K, Fonseka, CY, Rao, DA, Kelly, S, Goodman, SM, Tabechian, D, Hughes, LB, Salomon-Escoto, K, Watts, GFM, Jonsson, AH, Rangel-Moreno, J, Meednu, N, Rozo, C, Apruzzese, W, Eisenhaure, TM, Lieb, DJ, Boyle, DL, Mandelin, AM, Albrecht, J, Bridges, SL, Buckley, CD, Buckner, JH, Dolan, J, Guthridge, JM, Gutierrez-Arcelus, M, Ivashkiv, LB, James, EA, James, JA, Keegan, J, Lee, YC, McGeachy, MJ, McNamara, MA, Mears, JR, Mizoguchi, F, Nguyen, JP, Noma, A, Orange, DE, Rohani-Pichavant, M, Ritchlin, C, Robinson, WH, Seshadri, A, Sutherby, D, Seifert, J, Turner, JD, Utz, PJ, Boyce, BF, Dicarlo, E, Gravallese, EM, Gregersen, PK, Moreland, L, Firestein, GS, Hacohen, N, Nusbaum, C, Lederer, JA, Perlman, H, Pitzalis, C, Filer, A, Holers, VM, Bykerk, VP, Donlin, LT, Anolik, JH, Brenner, MB, Raychaudhuri, S |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2019 |
| المجموعة: | Oxford University Research Archive (ORA) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://ora.ox.ac.uk/objects/uuid:d2f8e218-c5dd-4f33-a3d4-de61cc5a1e9dTest; https://doi.org/10.1038/s41590-019-0378-1Test |
| DOI: | 10.1038/s41590-019-0378-1 |
| الإتاحة: | https://doi.org/10.1038/s41590-019-0378-1Test https://ora.ox.ac.uk/objects/uuid:d2f8e218-c5dd-4f33-a3d4-de61cc5a1e9dTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.58549B83 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41590-019-0378-1 |
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