Pathogenic stromal cells as therapeutic targets in joint inflammation

Knowledge of how the joint functions as an integrated unit in health and disease requires an understanding of the stromal cells populating the joint mesenchyme, including fibroblasts, tissue resident macrophages and endothelial cells. Physiological and pathological mechanisms in these mesenchymal cells that define the joint have begun to cast new light on why joint inflammation persists. In this review, we highlight how the shared embryological origins of fibroblasts and endothelial cells may shape the behaviour of these cell types in diseased adult tissues. We review the molecular mechanisms by which cells of mesenchymal origin sustain inflammation in the synovial membrane and tendons, highlighting the importance of recently discovered fibroblast subtypes and their associated cross talk with endothelial cells, tissue resident macrophages and leukocytes. Finally, we discuss how this knowledge shapes the future therapeutic landscape, emphasising the requirement for new strategies to address the pathogenic stroma and associated cross talk of leukocytes with cells of mesenchymal origin.