Autor(en)
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; Albrecht, Jennifer; Bridges, S. Louis; Buckley, Christopher D; Buckner, Jane H; Dolan, James; Guthridge, Joel M; Gutierrez-Arcelus, Maria; Ivashkiv, Lionel B; James, Eddie A; James, Judith A; Keegan, Josh; Lee, Yvonne C; McGeachy, Mandy J; McNamara, Michael A; Mears, Joseph R; Mizoguchi, Fumitaka; Nguyen, Jennifer P; Noma, Akiko; Orange, Dana E; Rohani-Pichavant, Mina; Ritchlin, Christopher; Robinson, William H; Seshadri, Anupamaa; Sutherby, Danielle; Seifert, Jennifer; Turner, Jason D; Utz, Paul J
Titel
Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
Teil von
  • Nature immunology, 2019-07-01, Vol.20 (7), p.928
Ort / Verlag
NEW YORK: NATURE PUBLISHING GROUP
Links zum Volltext
Quelle
Web of Science
Beschreibungen
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 Tcells, 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(hi) sublining fibroblasts, IL1B(+) pro-inflammatory monocytes, ITGAX(+)TBX21(+) autoimmune-associated B cells and PDCD1(+) peripheral helper T (T-PH) cells and follicular helper T (T-FH) cells. We defined distinct subsets of CD8(+)Tcells characterized by GZMIK(+), GZMB(+), and GNLY(+) phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed 1L6 expression to THYl(+)HLA-DRA(hi) fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

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