Session Title: T cell Biology in Rheumatoid Arthritis and Other Arthritis
Session Type: Abstract Submissions (ACR)
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that leads to progressive destruction of cartilage and bone. IL-22 and IL-22-producing T helper cells are elevated in RA patients, suggesting a role for this cytokine in the pathogenesis of this disease. Interestingly, IL-22 is a dual cytokine with both proinflammatory and anti-inflammatory properties, and therefore its exact role in RA pathology requires further investigation.
The aim of this study was to elucidate the role of IL-22 in the initiation and severity of a spontaneous model of experimental arthritis by using gene knockout mice and neutralizing antibodies for IL-22.
IL-1Ra-deficient mice develop spontaneous arthritis due to excess IL-1 signaling, and we previously demonstrated the importance of IL-17 and Th17 cells in this model (Koenders, Arthritis Rheum 2008). To investigate the role of IL-22 in this Th17-dependent arthritis model, we compared IL-1Ra-/- x IL-22+/+ mice to mice lacking both IL-1Ra and IL-22. Paw joint swelling was scored weekly, and mice were sacrificed at the age of fifteen weeks. In addition, IL-1Ra-deficient mice were treated for 4 weeks with anti-IL-22 neutralizing antibodies administered after onset of arthritis to inhibit disease progression.
Mice deficient for IL-1Ra and IL-22 showed reduced arthritis development, reaching a disease incidence of only 54% compared to an incidence of 93% in IL-1Ra-/- x IL-22+/+ mice. In addition, macroscopically scored joint swelling (scale 0 to 4) of mice that did develop arthritis was significantly reduced from 1,83 for the IL-22+/+ mice, to 1,27 for the IL-22-deficient mice. The reduction of inflammation was confirmed by histological analysis, that also showed protection against cartilage damage. Furthermore, significantly reduced bone damage was observed in IL-22 deficient mice as determined by X-ray analysis. Finally, IL-1Ra-deficient mice treated with anti-IL-22 antibodies after the clinical onset of arthritis showed reduced progression on inflammation and significant inhibition on bone erosion. This indicates that not only the onset but also the progression of arthritis in this Th17-driven arthritis model is dependent on IL-22.
These findings suggest that the Th17 cytokine IL-22 plays an important role both in the initiation and augmentation of Th17-dependent experimental arthritis, and might therefore be an interesting new target in RA treatment.
D. M. Roeleveld,
M. M. Helsen,
L. van den Bersselaar,
W. B. van den Berg,
M. I. Koenders,
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