Deconstruction of tophi and synovium defines SPP1+ macrophages involved in extracellular matrix remodelling in gout
Authors' conclusion
This study reveals a novel macrophage population (SPP1+/MMP9+/CHI3L1+) with dual immunomodulatory and matrix-remodelling capabilities, exclusively present in tophus tissues but absent in intercritical gout synovium or flare-associated synovial fluid.
Study context
- Population
- Patients with intercritical gout (without tophi) and tophaceous gout; synovial tissue and tophi44,221 synovial tissue cells
- Comparison
- Tophaceous gout vs intercritical gout synovial tissue
- Outcome
- Immune-stromal cell populations in tophus formation
Methodological detailssingle-cell transcriptomic profiling, spatial transcriptomics, immunofluorescence and flow cytometry validation, Mendelian randomisation
- Single-cell transcriptomic profiling
- Spatial transcriptomics
- Immunofluorescence and flow cytometry validation
- Mendelian randomisation
Main finding
As reported in the abstract
- SPP1+/MMP9+/CHI3L1+ macrophages within the corona zone exclusive to tophaceous gout, with extracellular matrix regulation genes, enhanced integrin-mediated interactions with stromal cells and transitional potential towards osteoclast differentiation
- Coexpression of fibroblast marker S100A4 and COL6A2 in these macrophages suggested a fibroblast-like phenotype
- Distinct CD4+ T-cell profiles between disease states: shift from inflammatory to immune-regulatory subsets during tophus development
Original publication
Deconstruction of tophi and synovium defines SPP1+ macrophages involved in extracellular matrix remodelling in gout. Ann Rheum Dis. Published 17 October 2025. doi:10.
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