Cytokine-induced PD-L1 and PD-L2 expression is preserved but reverse signalling is altered in rheumatoid arthritis fibroblast-like synoviocytes
Authors' conclusion
Cytokine-induced PD-L1 and PD-L2 expression is preserved in FLS from established RA but PD1-ligand signalling is altered, potentially contributing to the loss of immune regulation in RA.
Study context
- Population
- Primary fibroblast-like synoviocytes (FLS) cell lines from synovial tissue of patients with established rheumatoid arthritis (RA) or non-inflammatory (NI) controls
- Comparison
- RA-FLS vs NI-FLS
- Outcome
- PD-L1 and PD-L2 expression on FLS and PD1 reverse signalling
Methodological detailsin vitro, CRISPR/Cas9 knockout, total mRNA sequencing, analysis of publicly available RNA-sequencing datasets
- In vitro
- CRISPR/Cas9 knockout
- Total mRNA sequencing
- Analysis of publicly available RNA-sequencing datasets
Main finding
As reported in the abstract
- TNF and IFNγ induced PD-L1 expression up to fourfold vs unstimulated FLS; IL-4 and TGF-β had no effect
- fourfold
- Soluble PD1-induced reverse signalling altered expression of threefold more genes in NI-FLS vs RA-FLS
- threefold
Further findings
PD-L1 and PD-L2 expression by synovial pathotype (public RNA-seq datasets)
- Early RA: significantly higher in lymphoid vs myeloid and fibroid pathotypes
- Established RA: trend towards higher levels in FLS from lymphocyte-rich vs lymphocyte-poor tissue
Original publication
Cytokine-induced PD-L1 and PD-L2 expression is preserved but reverse signalling is altered in rheumatoid arthritis fibroblast-like synoviocytes. Arthritis Res Ther. Published 2 June 2026. doi:10.
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