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

Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium

Research output: Contribution to journalArticle

30 Citations (Scopus)

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-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 + 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 hi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

Original languageEnglish (US)
JournalNature Immunology
DOIs
StatePublished - Jan 1 2019

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Rheumatoid Arthritis
Joints
RNA Sequence Analysis
HLA-DR alpha-Chains
Monocytes
Fibroblasts
Population
B-Lymphocytes
Synovial Fluid
T-Lymphocyte Subsets
Helper-Inducer T-Lymphocytes
Osteoarthritis
Interleukin-6
Flow Cytometry
RNA
Inflammation
T-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium. / Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. In: Nature Immunology. 2019.
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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-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 + 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 hi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.",
author = "{Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium} and Fan Zhang and Kevin Wei and Kamil Slowikowski and Fonseka, {Chamith Y.} and Rao, {Deepak A.} and Stephen Kelly and Goodman, {Susan M.} and Darren Tabechian and Hughes, {Laura B.} and Karen Salomon-Escoto and Watts, {Gerald F.M.} and Jonsson, {A. Helena} and Javier Rangel-Moreno and Nida Meednu and Cristina Rozo and William Apruzzese and Eisenhaure, {Thomas M.} and Lieb, {David J.} and Boyle, {David L.} and Mandelin, {Arthur M.} and Jennifer Albrecht and Bridges, {S. Louis} and Buckley, {Christopher D.} and Buckner, {Jane H.} and James Dolan and Guthridge, {Joel M.} and Maria Gutierrez-Arcelus and Ivashkiv, {Lionel B.} and James, {Eddie A.} and James, {Judith A.} and Josh Keegan and Lee, {Yvonne C.} and McGeachy, {Mandy J.} and McNamara, {Michael A.} and Mears, {Joseph R.} and Fumitaka Mizoguchi and Nguyen, {Jennifer P.} and Akiko Noma and Orange, {Dana E.} and Mina Rohani-Pichavant and Christopher Ritchlin and Robinson, {William H.} and Anupamaa Seshadri and Danielle Sutherby and Jennifer Seifert and Turner, {Jason D.} and Utz, {Paul J.} and Boyce, {Brendan F.} and Edward DiCarlo and Gravallese, {Ellen M.}",
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Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. / Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium.

In: Nature Immunology, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium

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AU - Wei, Kevin

AU - Slowikowski, Kamil

AU - Fonseka, Chamith Y.

AU - Rao, Deepak A.

AU - Kelly, Stephen

AU - Goodman, Susan M.

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AU - Apruzzese, William

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AU - Gutierrez-Arcelus, Maria

AU - Ivashkiv, Lionel B.

AU - James, Eddie A.

AU - James, Judith A.

AU - Keegan, Josh

AU - Lee, Yvonne C.

AU - McGeachy, Mandy J.

AU - McNamara, Michael A.

AU - Mears, Joseph R.

AU - Mizoguchi, Fumitaka

AU - Nguyen, Jennifer P.

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AU - Orange, Dana E.

AU - Rohani-Pichavant, Mina

AU - Ritchlin, Christopher

AU - Robinson, William H.

AU - Seshadri, Anupamaa

AU - Sutherby, Danielle

AU - Seifert, Jennifer

AU - Turner, Jason D.

AU - Utz, Paul J.

AU - Boyce, Brendan F.

AU - DiCarlo, Edward

AU - Gravallese, Ellen M.

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N2 - 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 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 + 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 hi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

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