IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis

The origin and role of IL-17, a T-cell derived cytokine, in cartilage and b one destruction during rheumatoid arthritis (RA) remain to be clarified. In human ex vivo models, addition of IL-17 enhanced IL-6 production and colla gen destruction, and inhibited collagen synthesis by RA synovium explants. On mouse cartilage, IL-17 enhanced cartilage proteoglycan loss and inhibite d its synthesis. On human RA bone explants, IL-17 also increased bone resor ption and decreased formation. Addition of IL-1 in these conditions increas ed the effect of IL-17. Blocking of bone-derived endogenous IL-17 with spec ific inhibitors resulted in a protective inhibition of bone destruction. Co nversely, intra-articular administration of IL-17 into a normal mouse joint induced cartilage degradation. In conclusion, the contribution of IL-17 de rived from synovium and bone marrow T cells to joint destruction suggests t he control of IL-17 for the treatment of RA.