The role of IL-23 in joint disease

The myeloid cell-derived cytokine interleukin (IL-23) has been identified as an orchestrator of chronic inflammatory disease. IL-23 is instrumental in the activation of effector T cells and innate lymphoid cells, which in turn allow the mobilization of pro-inflammatory macrophages and neutrophils from the bone marrow and the initiation of inflammation in the joints, the gut and the skin. While the role of IL-23 in mounting chronic skin inflammation in the context of psoriasis is well established, increasing evidence suggests that also colitis and psoriatic arthritis are controlled by IL-23. Psoriasis, Crohn’s disease and psoriatic arthritis share a common genetic link to IL-23 receptor haplotypes and a therapeutic response to neutralization of IL-23. By controlling the expression of downstream effector cytokines IL-17A and TNFa, IL-23 triggers entheseal and synovial inflammation in patients with psoriatic arthritis by activating T cells and permitting the influx of macrophages and neutrophils into entheses and joints. Furthermore, IL-23 also influences structural changes in the joints of patients with psoriatic arthritis by enhancing osteoclast mediated bone resorption leading to bone erosion, as well as by modulating bone-forming osteoblasts resulting in bony spur formation and ankylosis. In summary, IL-23 represents a highly specialized inflammatory mediator, which is involved in the communication of inflammation across organs. IL-23 is positioned at the initiation point of a pro-inflammatory cytokine cascade that precipitates the development of psoriatic arthritis.