The critical role of interleukin-23 in spondyloarthropathy

• Excess production of IL-23 occurs in SpA.
• IL-23 is produced in the intestine and skin during SpA.
• HLA-B27 misfolding also results in IL-23 production.
• Spondyloarthropathy is associated with IL-23R polymorphisms.
• Entheses contain a novel population of IL-23 responsive cells.

The spondyloarthropathies represent highly enigmatic conditions and although their clinical features, anatomical distribution of disease and genetic predisposing factors have been known for some time, a unified concept of the basic pathobiology underlying these illnesses has remained undefined. Recently progress has been made because numerous independent studies have converged upon IL-23 as a central cytokine in spondyloarthropathy and the mechanism and sites of action of this cytokine have now become much clearer. These findings enable the rational design of therapeutic strategies which it is hoped will profoundly modify the progression of these diseases. We will review the anatomical sites affected and the evidence for the importance of IL-23 in these conditions, before drawing these lines of investigation together to propose a model for the unified understanding of spondyloarthropathy.