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

## TL;DR

This study uses spatial transcriptomics to map immune and stromal cell interactions in the synovium of children with juvenile idiopathic arthritis, revealing disease-specific patterns and structures.

## Contribution

The study introduces a new computational pipeline for spatial colocalization analysis and identifies unique immune-stromal interactions in JIA synovial tissue.

## Key findings

- Endothelial-fibroblast interactions are mediated by NOTCH signaling in JIA synovium.
- A CXCL9/CXCR3 signaling axis connects inflammatory macrophages and CD8+ T cells in JIA.
- Tertiary lymphoid structures in JIA are marked by CXCL13/CXCR5 and CCL19 signaling.

## 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.

Spatial transcriptomics reveals immune–stromal niches and disease-specific interactions in juvenile idiopathic arthritis synovial tissue.