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

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

<p>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 f...

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Main Authors: 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
Format: Journal article
Published: Nature Research 2019
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Summary:<p>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: <em>THY1(CD90)</em><em><sup>+</sup></em><em>HLA-DRA</em><sup>hi</sup> sublining fibroblasts, <em>IL1B</em><sup>+</sup> pro-inflammatory monocytes, <em>ITGAX</em><sup>+</sup><em>TBX21</em><sup>+</sup> autoimmune-associated B cells and <em>PDCD1</em><sup>+</sup> peripheral helper T (T<sub>PH</sub>) cells and follicular helper T (T<sub>FH</sub>) cells. We defined distinct subsets of CD8<sup>+</sup> T cells characterized by <em>GZMK</em><sup>+</sup>, <em>GZMB</em><sup>+</sup>, and <em>GNLY</em><sup>+</sup> phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed <em>IL6</em> expression to <em>THY1</em><sup>+</sup><em>HLA-DRA</em><sup>hi</sup> fibroblasts and <em>IL1B</em> production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.</p>

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