The role of innate immune cells in tissue inflammation in spondyloarthritis

It is increasingly clear that the two most common forms of chronic inflammatory arthritis, rheumatoid arthritis and spondyloarthritis, have a distinct pathophysiology. Where failure of the acquired immune system is a major contributor for rheumatoid arthritis, this is not the case for spondyloarthritis. We thus investigated mechanisms and cells related to the innate, rather than the acquired, immune system in spondyloarthritis. We have analyzed tissue macrophages on parameters as cytokine production and phenotype of polarization. And we show that there is no distinct macrophage polarization pattern that can be related to spondyloarthritis-pathophysiology. Looking at mast cells, however, we have found a rationale for mast cell targeting in spondyloarthritis. We have confirmed the effectiveness of a mast cell inhibitory strategy in patients with peripheral spondyloarthritis. And we have provided cell biological evidence of a mast cell/IL-17 axis, that may be involved in spondyloarthritis. In this newly discovered axis mast cells take up exogenous IL-17, store it and are able to release the inflammatory cytokine back to the extracellular milieu. It remains to be determined what the exact origin is for the pathological role of mast cells and how the new mast cell/IL-17 axis fits in the pathophysiology of spondyloarthritis.