ArticleNature immunology2026
Spatial patterning of fibroblast TGFβ signaling underlies treatment resistance in rheumatoid arthritis.
Article in Nature immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Protective role of summer acupoint application therapy on weather-triggered rheumatoid arthritis flares.One health (Amsterdam, Netherlands) · 2026Article
- Immune-mediated rheumatoid arthritis: from single-cell genomics to new therapies.Nature immunology · 2026Review
- BCAT2 links branched-chain amino acids metabolism to interferon signaling to sustain macrophage inflammation.Nature immunology · 2026Article
- When inflammation is not the driver: Pauci-immune synovitis and the stromal basis of refractory arthritis.EULAR rheumatology open · 2026Review
- Multi-Technique Integration Identifies O-GlcNAc Transferase in Fibroblast-Like Synoviocytes as a Therapeutic Target for Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatial Orchestration of Skin Fibrosis by a CD8+ T cell- Myofibroblast Axis.bioRxiv : the preprint server for biology · 2026Article
- Targeting fibroblasts in immune mediated inflammatory diseases: a cellular basis for cure?Rheumatology (Oxford, England) · 2026Review
- Reciprocal Regulation of GLI1 and GLI3 Fine Tunes the Pathogenic Behavior of Synovial Fibroblasts in Rheumatoid Arthritis.International journal of rheumatic diseases · 2026Article
- Prenatal and Postnatal Determinants of Outcome in Neonates with Omphalocele: A 25-Year Single-Center Cohort Study.Journal of clinical medicine · 2026Article
- Inflammation-Driven Lymphoid Structures: Organization, Function, and Clinical Impact Across Autoimmunity, Cancer, and Checkpoint Toxicity.Immunological reviews · 2026Review
- A human synovial tendon-on-a-chip models key features of peritendinous adhesions and offers a new approach methodology for testing anti-fibrotic drugs.bioRxiv : the preprint server for biology · 2026Article
- Fibroblast TGFβ drives treatment-refractory RA.Nature reviews. Rheumatology · 2026Article
- Bridging the Precision Gap in Rheumatoid Arthritis: Spatial Transcriptomics, Spatial Proteomics, and Artificial Intelligence in Precision Health.Biomedicines · 2026Review
- Pathogenic Drivers of Difficult-to-Treat Rheumatoid Arthritis: Synovium and Beyond.International journal of molecular sciences · 2026Review
- Spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis.JCI insight · 2026Article
- Failed resolution as a mechanistic basis of difficult-to-treat rheumatoid arthritis: stromal-myeloid crosstalk in the synovium and emerging resolution-restoring therapies.Frontiers in immunology · 2026Review
- Injectable Hyaluronic Acid-Functionalized Nanocomposite Hydrogel for Targeted Rheumatoid Arthritis Therapy via Concurrent ROS Attenuation and Macrophage Repolarization.International journal of nanomedicine · 2026Article
- From Systemic Autoimmunity to the Local Immune Niche of the Synovium: New Insights into the Development of Rheumatoid Arthritis.Journal of inflammation research · 2026Review
- Synovial matrix turnover controls immune cell spatial patterning in inflammation resolution.Molecular systems biology · 2025Article
- Fibrosis in Immune-Mediated and Autoimmune Disorders.Journal of clinical medicine · 2025Review
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33 authors.
Funding
Abstract
Treatment-refractory rheumatoid arthritis (RA) is a major unmet need, and the underlying mechanisms are poorly understood. To identify molecular determinants of refractory RA, we performed spatial transcriptomic profiling on synovial tissue biopsy samples taken 6 months before and after treatment. In the baseline biopsy samples of non-remitting patients, we identified increased fibrogenic signaling within vascular tissue niches, marked by high fibroblast COMP expression. We uncovered a role of endothelial-derived Notch signaling as an upstream regulator of fibroblast transforming growth factor beta (TGFβ) signaling via its opposing ability to induce TGFβ isoform expression while suppressing TGFβ receptors, generating a proximal-to-distal gradient of TGFβ sensitivity that can be altered with disruption of steady-state Notch signaling. In posttreatment biopsy samples, we observed significant immune depletion with expansion of fibrogenic niches, a process that can be reversed by inhibition of Notch and TGFβ signaling in RA patient-derived organoids. Collectively, our data implicate targeting of TGFβ signaling to prevent exuberant synovial tissue fibrosis as a potential therapeutic strategy for refractory RA.
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