ITGA5+ synovial fibroblasts orchestrate proinflammatory niche formation by remodelling the local immune microenvironment in rheumatoid arthritis
Authors' conclusion
We demonstrate that ITGA5+ synovial fibroblasts might regulate the RA progression by inducing the differentiation of CXCL13hiPD-1hi TPHs and remodelling the proinflammatory microenvironments.
Study context
- Population
- Synovial tissues of patients with OA, rheumatoid arthritis (RA) in sustained remission and active RA; PEAC and R4RA cohorts; Collagen-induced arthritis (CIA) mice
- Comparison
- OA vs RA in sustained remission vs active RA
Methodological detailssingle-cell and spatial transcriptomics, deconvolution validation in PEAC and R4RA cohorts, cell coculture, adoptive transfer in CIA mice
- Single-cell and spatial transcriptomics
- Deconvolution validation in PEAC and R4RA cohorts
- Cell coculture
- Adoptive transfer in CIA mice
Main finding
As reported in the abstract
- Novel tissue-remodelling CD45-CD31-PDPN+ITGA5+ synovial fibroblast population identified, with unique transcriptome of POSTN, COL3A1, CCL5 and TGFB1, enriched in immunoregulatory pathways
- Subset upregulated in active and lympho-myeloid type of RA, associated with increased risk of multidrug resistance
- Transforming growth factor (TGF)-β1 might participate in the differentiation of this subset
- ITGA5+ synovial fibroblasts might occur in early inflammation and induce differentiation of CXCL13hiPD-1hi TPHs from naïve CD4+ T cells by secreting TGF-β1
- Intra-articular injection of ITGA5+ synovial fibroblasts exacerbates RA development and upregulates TPHs in CIA mice
Original publication
ITGA5+ synovial fibroblasts orchestrate proinflammatory niche formation by remodelling the local immune microenvironment in rheumatoid arthritis. Ann Rheum Dis. Published 2 January 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →