ATAC-seq of synovial tissues from mice with Antigen Induced Arthritis (AIA) showing distinct hallmarks of synovitis heterogeneity
Joint pathology in rheumatoid arthritis is broadly classified as fibroblast-rich, myeloid-rich, or lymphoid-rich synovitis. How these pathotypes evolve is unknown. Based on the clinical efficacy of biological medicines and targeted inhibitors, we hypothesise that cytokines instruct this process, affecting the rate of onset, severity, and course of disease. These include cytokine signals that define the organisation and maintenance of lymphocyte sentinels in lymphoid-rich synovitis, and others that guide a pauci-immune pathology involving activated stromal cells in fibroblast-rich synovitis.  With a long-standing interest in the IL-6 cytokine family, we have identified distinct roles for Jak-STAT signalling in shaping synovitis heterogeneity. Establishing new mouse models that mimic fibroblast-rich, myeloid-rich, and lymphoid-rich synovitis in humans, we propose that wild-type (WT), Il6ra-/-, and Il27ra-/- mice with AIA share hallmarks of these pathotypes. The reported RNA-seq now profiles the transcriptional profile of synovitis in WT, Il6ra-/-, and Il27ra-/- mice with AIA and provides datasets captured at day-3 and day-10 AIA reflecting early and established disease.