Inamo Jun, Fierkens Roselyn, CLay Michael R, Jonsson Anna Helena, Lin Clara, Hayes Kari, Rogers Nathan, Leach Heather, Yomogida Kentaro
Department of Biomedical Informatics, Center for Health Artificial Intelligence, University of Colorado School of Medicine, Aurora, CO, United States of America.
Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, United States of America.
medRxiv. 2025 Aug 8:2025.08.05.25332835. doi: 10.1101/2025.08.05.25332835.
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 signalling, 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 dendritic cells, analogous to those observed in other autoimmune diseases. Finally, comparative analysis with rheumatoid arthritis reveals JIA-enriched cell states, including and 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.
Arthritis Rheumatol. 2025-8
Cochrane Database Syst Rev. 2024-2-9