Cytokine-directed cellular cross-talk imprints synovial pathotypes in rheumatoid arthritis
An erratum to this article was published (Ann Rheum Dis, Nov 2023 ↗)
Authors' conclusion
Our study highlights the role of cytokine-activated FLS in orchestrating inflammation-associated synovial pathotypes providing novel insights into disease mechanisms of RA.
Study context
- Population
- Patients with rheumatoid arthritis (RA): Fibroblast-like synoviocytes (FLS) and autologous peripheral CD4+ T cells
- Comparison
- Cytokine-activated vs unstimulated FLS co-cultured with autologous peripheral CD4+ T cells
- Outcome
- FLS-T cell interaction and synovial pathotype signatures
Methodological detailsautomated high-content fluorescence microscopy, flow cytometry, RNA-Seq, integration with public transcriptomic data, knock-down experiments
- Automated high-content fluorescence microscopy
- Flow cytometry
- RNA-Seq
- Integration with public transcriptomic data
- Knock-down experiments
Main finding
As reported in the abstract
- Cytokine stimulation, especially TNF-α, enhanced FLS-T cell interaction, causing contact-dependent T cell activation, proliferation and differentiation
- Cytokine-activated FLS signatures significantly enriched in lymphoid-rich or leucocyte-rich RA synovial pathotypes, most prominent for TNF-α
- FLS cytokine signatures correlated with number of infiltrating CD4+ T cells in RA synovial tissue
- ICAM1 on FLS identified as important mediator of TNF-mediated FLS-T cell interaction; ICAM1 and its receptors overexpressed in TNF-treated FLS and co-cultured T cells
- Knock-down of ICAM1 in FLS reduced TNF-mediated FLS-T cell interaction
Original publication
Cytokine-directed cellular cross-talk imprints synovial pathotypes in rheumatoid arthritis. Ann Rheum Dis. Published 21 June 2023. doi:10.
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