Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
Spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis
Jun Inamo, Roselyn Fierkens, Michael R. Clay, Anna Helena Jonsson, Clara Lin, Kari Hayes, Nathan Rogers, Heather Leach, Kentaro Yomogida
Jun Inamo, Roselyn Fierkens, Michael R. Clay, Anna Helena Jonsson, Clara Lin, Kari Hayes, Nathan Rogers, Heather Leach, Kentaro Yomogida
View: Text | PDF
Research Article Immunology

Spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis

  • Text
  • PDF
Abstract

Juvenile idiopathic arthritis (JIA) is the most prevalent chronic inflammatory arthritis of childhood, yet the spatial organization in the synovium remains poorly understood. Here, we perform subcellular-resolution spatial transcriptomic profiling of synovial tissue from patients with active JIA. We identify diverse immune and stromal cell populations and reconstruct spatially defined cellular niches. Applying a newly developed spatial colocalization analysis pipeline, we uncover microanatomical structures, including endothelial-fibroblast interactions mediated by NOTCH signaling, and a CXCL9/CXCR3 signaling axis between inflammatory macrophages and CD8+ T cells, alongside the characterization of other resident macrophage subsets. We also detect and characterize tertiary lymphoid structures marked by CXCL13/CXCR5 and CCL19-mediated signaling from Tph cells and immunoregulatory DCs, analogous to those observed in other autoimmune diseases. Finally, comparative analysis with rheumatoid arthritis reveals JIA-enriched cell states, including NOTCH3+ and CXCL12+ sublining fibroblasts, suggesting potentially differential inflammatory programs in pediatric versus adult arthritis. These findings provide a spatially resolved molecular framework of JIA synovitis and introduce a generalizable computational pipeline for spatial colocalization analysis in tissue inflammation.

Authors

Jun Inamo, Roselyn Fierkens, Michael R. Clay, Anna Helena Jonsson, Clara Lin, Kari Hayes, Nathan Rogers, Heather Leach, Kentaro Yomogida

×

Figure 11

Comparative analysis of JIA and RA synovium using integrated spatial-transcriptomic and scRNA-Seq data.

Options: View larger image (or click on image) Download as PowerPoint
Comparative analysis of JIA and RA synovium using integrated spatial-tra...
(A) Cell type level label transfer results, where RA synovium scRNA-Seq was used as the reference and JIA synovium Xenium data as the query. RA-derived annotations were transferred to individual JIA cells using a k-nearest neighbors (kNN) approach in the integrated latent space. (B) Match rate between transferred RA-synovium cell types and our original JIA-synovium-based annotations. Matrix shows percentage overlap between each transferred and original broad cell type. (C) Cell clustering in the integrated latent space. UMAP visualizations of both JIA (Xenium) and RA (scRNA-Seq) cells are colored by newly defined shared clusters. (D) CNA identifies integrated-space clusters that are expanded or depleted in JIA synovium relative to RA synovium. Sex and disease duration were adjusted for, while age was excluded from covariates due to its collinearity with disease status, reflecting the distinct age of onset between RA and JIA. Left: Spatial visualization of cells colored by neighborhood correlation (red, expanded in JIA; blue, depleted). Middle: Violin plots showing distribution of neighborhood correlations for each integrated cluster. Only clusters with cells either of positive or negative correlation > 80% are shown. Right: Bar plots showing cell-type composition of each cluster in RA (left) and JIA (right) synovium. For each cluster, the most abundant original cell type (from either RA or JIA) is annotated with text in each bar. Center bar plot showing relative proportion of cells derived from JIA versus RA within each cluster (orange, JIA; blue, RA). (E) Box plots showing the lineage-normalized proportion of cell clusters across individual samples, stratified by condition (JIA versus RA synovium). P values were calculated using Wilcoxon rank-sum tests. Box plots showing the median, interquartile range, and 1.5× interquartile range (IQR) whiskers.

Copyright © 2026 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts