A novel subset of fibrocyte-like cells in synovial fluid communicate with CD8 T cells and shape the local inflammatory milieu in Juvenile Idiopathic Arthritis (JIA). (HUM3P.253)

Abstract

Abstract We reported previously that children with JIA carry senescent CD31+CD8+ T cells disproportionate with age. Such cells are inflammatory effectors via CD31-driven TCR-independent activation pathway. Here, we hypothesized that these T cells interact with non-hematopoietic cells in the synovial space to perpetuate joint inflammation. JIA patients medically indicated to undergo arthrocentesis were recruited. Synovial aspirates were screened by flow cytometry, and short-term cultures were established. Results showed two subsets of plastic-adherent fibrocyte-like cells (FLC). About 75% were procollagen-CD45-CD14- cells that variably expressed CD34. The other ~25% were procollagen+CD45+CD14+IL17RA+ CD34- FLC; a finding unlike similar cells reported for adult-onset rheumatoid arthritis. FLC exposed to rIL-17 and/or rTNFα induced production of MMPs that were reversed with corticosteroid, TNFi, anti-IL6R, or experimental NFkB inhibitors. Co-culture of FLC with autologous CD8 T cells resulted in production of the same array of MMPs and inflammatory cytokines that were partially blocked by neutralizing anti-CD31 antibody. These results suggest a FLC-CD8 T cell communication circuit in the maintenance of joint inflammation in JIA. Further understanding of the regulation and/or the consequences of this local cell-cell interaction could shed light into the systemic complications of this childhood disease that impose lifelong health burden. [Supported by Nancy E Taylor Foundation and NIH].