ArticleFrontiers in immunology2026
Reduced fibroblast-derived IGFBP5 is associated with pathogenic synovial fibroblast states and altered macrophage polarization in rheumatoid arthritis.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Rheumatoid arthritis (RA) is characterized by synovial inflammation, synovial fibroblast (SF) activation, and joint destruction. Activated SFs acquire proliferative and invasive properties and interact with macrophages to maintain the inflammatory microenvironment. However, endogenous factors regulating fibroblast activation and fibroblast-macrophage communication in RA are not fully understood. In this study, we examined the expression of insulin-like growth factor binding protein 5 (IGFBP5) in RA synovium at single-cell resolution and investigated its role in SF activation and macrophage polarization. Methods: Single-cell RNA sequencing (scRNA-seq) datasets from normal and RA synovial tissues were reprocessed and integrated using Seurat and Harmony. Sample-level quality-control metrics and cellular composition were evaluated per sample. Donor-level pseudo-bulk analysis and external synovial transcriptomic datasets were used to validate IGFBP5 downregulation. Pseudotime analysis, SAVER imputation, RA-only CellChat analysis, and in silico IGFBP5 perturbation were performed. Disease-associated IGFBP5 expression was evaluated in a collagen-induced arthritis (CIA) mouse model, whereas IGFBP5 overexpression was examined Results: scRNA-seq analysis showed that IGFBP5 expression was reduced in RA synovial fibroblasts, particularly in inflammatory and fibrotic subclusters. Donor-level pseudo-bulk analysis supported lower IGFBP5 expression in RA fibroblasts, particularly in lining and sublining fibroblasts, and external datasets showed concordant reductions or downward trends. IGFBP5 expression was negatively associated with pathogenic fibroblast markers FAP and THY1 and positively associated with the homeostatic marker PRG4. In CIA mice, IGFBP5 expression was decreased in hyperplastic synovial tissues and CIA-derived synovial fibroblasts. Conclusions: Reduced IGFBP5 expression is associated with pathogenic fibroblast states in RA. IGFBP5 overexpression
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.