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

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.