ArticleScience translational medicine2025
Synovial tissue atlas in juvenile idiopathic arthritis reveals pathogenic niches associated with disease severity.
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Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21citing papers in PubMed
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21 citing papers in PubMed.
- Spatial multi‑omics identifies an SPP1+ macrophage‑driven anti‑apoptotic niche in osteoarthritis synovium via the SPP1‑CD44 axis.International journal of molecular medicine · 2026Article
- Synovial Fluid Immune Cell Landscape in Juvenile Idiopathic Arthritis.European journal of immunology · 2026Article
- Immune-mediated rheumatoid arthritis: from single-cell genomics to new therapies.Nature immunology · 2026Review
- Macrophages in fibrin-rich lining niche shape the rheumatoid pannus.Nature reviews. Rheumatology · 2026Article
- Efforts towards a precision medicine approach in juvenile idiopathic arthritis.Rheumatology (Oxford, England) · 2026Review
- Spatially resolved fetal and maternal cell contributions to severe preeclampsia across gestation.Science advances · 2026Article
- Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.Nature immunology · 2026Article
- Article
- How can innovative trials in juvenile idiopathic arthritis serve the unmet needs of patients?Arthritis research & therapy · 2026Review
- TAK1 inhibition restores p53 expression and suppresses inflammation and hyperplasia in JIA synovial fibroblasts.Rheumatology (Oxford, England) · 2026Article
- Synovial fluid potentiates local fibroblasts to drive monocyte activation in juvenile idiopathic arthritis.Arthritis research & therapy · 2026Article
- Altered B cell activation contributes to the immunopathogenesis of childhood arthritis-associated uveitis.Nature communications · 2026Article
- Spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis.JCI insight · 2026Article
- Evolving role of CD8Frontiers in immunology · 2026Review
- Exploratory analysis of neutrophil extracellular traps in synovial fluid and plasma from children with juvenile idiopathic arthritis.Frontiers in pediatrics · 2026Article
- Novel insights into the biology of childhood arthritis- lessons learned from the synovium.Arthritis research & therapy · 2025Review
- The ontogeny of myeloid-stromal synovial tissue niches in rheumatoid arthritis.Research square · 2025Article
- Looking to the new horizon in rheumatology research.Nature reviews. Rheumatology · 2025Article
- The ontogeny of myeloid-stromal synovial tissue niches in rheumatoid arthritis.bioRxiv : the preprint server for biology · 2025Article
- Subcellular spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis.medRxiv : the preprint server for health sciences · 2025Article
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Authors and funding
46 authors.
Chrissy BoltonInfection, Immunity, and Inflammation Research and Teaching Department, University College London (UCL) Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.ORCID 0000-0003-0240-3244
Christopher B MahonyDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0000-0003-4487-2540
Elizabeth ClayDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.
Patricia Reis NisaDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0009-0006-2255-9958
Søren LomholtDepartment of Biomedicine, Aarhus University, Aarhus, Denmark, DK-8000.ORCID 0000-0001-5916-4219
Annie HacklandDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0009-0008-6765-7345
Paulynn S ChinDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0000-0003-1600-3508
Charlotte G SmithDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0009-0008-2021-546X
Vicky AlexiouDepartment of Ageing, Rheumatology and Regenerative Medicine, Division of Medicine, UCL, London WC1E 6JF, UK.ORCID 0009-0000-8723-6320
Huong D NguyenInfection, Immunity, and Inflammation Research and Teaching Department, University College London (UCL) Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.ORCID 0000-0003-1524-8028
Manigandan ThyagarajanBirmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham B15 2TG, UK.ORCID 0009-0009-4502-2805
Zishan SheikhBirmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham B15 2TG, UK.
Penny DavisBirmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham B15 2TG, UK.
Samantha ChippingtonNIHR Biomedical Research Centre at Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Sandrine Compeyrot-LacassagneNIHR Biomedical Research Centre at Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.ORCID 0000-0001-5533-7493
Sunit DavdaNIHR Biomedical Research Centre at Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.ORCID 0000-0002-9122-1057
Charlene FoleyNIHR Biomedical Research Centre at Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
Inga TurtsevichNIHR Biomedical Research Centre at Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.ORCID 0000-0002-3874-9186
Benjamin IngledowDepartment of Ageing, Rheumatology and Regenerative Medicine, Division of Medicine, UCL, London WC1E 6JF, UK.
Klaudia KupiecNIHR Biomedical Research Centre at Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.ORCID 0000-0002-5673-173X
James KellyDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0009-0008-5901-1077
Megan M HanlonDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-6527-8818
Edward DiCarloDepartment of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY 10021, USA.ORCID 0000-0001-5775-3167
Luke J JonesDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0009-0007-2344-7277
Samantha L SmithCentre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK.ORCID 0000-0002-4108-8497
Stephen EyreCentre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK.ORCID 0000-0002-1251-6974
Georgiana NeagDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.
Samuel KembleDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0000-0002-3359-7718
Roopa MadhuDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Mukta G PalshikarDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1179-7903
Ilya KorsunskyDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-4848-3948
Ce GaoDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-9804-261X
Miles TranDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Calliope DendrouKennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK.ORCID 0000-0003-1179-4021
Christopher D BuckleyKennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK.ORCID 0000-0001-6924-6402
Mark C ColesKennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK.ORCID 0000-0001-8079-9358
Karim RazaDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0000-0003-1570-1232
MAPJAG Study Group
Ellen GravalleseDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-0981-0996
Andrew FilerDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0000-0001-8164-6249
Kevin WeiDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1821-167X
Eslam Al-AbadiBirmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham B15 2TG, UK.
Elizabeth C RosserDepartment of Ageing, Rheumatology and Regenerative Medicine, Division of Medicine, UCL, London WC1E 6JF, UK.ORCID 0000-0003-4800-4695
Lucy R WedderburnInfection, Immunity, and Inflammation Research and Teaching Department, University College London (UCL) Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.ORCID 0000-0002-7495-1429
Adam P CroftDepartment of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.ORCID 0000-0002-9487-0511
Multiomic Analysis of Paediatric Joint and Gut inflammation (MAPJAG) study group
Funding
Pathogenic fibroblast differentiation in rheumatoid arthritisK08AR077037 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI WEI, KEVIN S · 2020 to 2024
$799kUsing high dimensional molecular data to decipher gene dynamics underlying pathogenic synovial fibroblastsK01AR078355 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI KORSUNSKY, ILYA · 2021 to 2025
$442kMedical Research Council MR/R013926/1Medical Research Council MR/W028557/1Medical Research Council MR/X001393/1NIAMS NIH HHS K01 AR078355NIAMS NIH HHS K08 AR077037Versus Arthritis 20164Versus Arthritis 22084Versus Arthritis 22710Versus Arthritis 23153
Abstract
Precision application of targeted therapies is urgently needed to improve long-term clinical outcomes for children affected by inflammatory arthritis, known as juvenile idiopathic arthritis (JIA). Progress has been hampered by our limited understanding of the cellular basis of inflammation in the target tissue of the disease, the synovial membrane. Here, we analyzed biopsies from the inflamed joints of treatment-naïve children with JIA, early in the course of their disease, using single-cell RNA sequencing, multiplexed immunofluorescence, and spatial transcriptomics to establish a cellular atlas of the JIA synovium. We identified distinct spatial tissue niches, composed of specific stromal and immune cell populations. In addition, we localized genes linked to arthritis severity and disease risk to effector cell populations, including tissue resident
Indexed as
Arthritis, JuvenileSeverity of Illness IndexSynovial MembraneAdolescentChildChild, PreschoolFemaleHumansInflammationMacrophagesMaleMyeloid CellsSingle-Cell AnalysisStromal CellsTranscriptome
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