Rheumatoid arthritis is a debilitating disease afflicting millions of Americans;it also causes a significant economic burden. Recently this disease has been associated with aberrant T helper-17 (Th17) responses. Adaptive immune responses have long been thought to be dominated by either Th1 or Th2 cells. More recently, however, Th17 cells have been discovered;these cells are critical in defense against many extracellular bacteria and fungi, but they have also been found to drive a number of inflammatory and autoimmune diseases, including rheumatoid arthritis. IL-17 (aka IL-17A) is the signature cytokines of Th17 cells and the importance of this cytokine in arthritis has been revealed with mouse models. Mice lacking IL-17A exhibit an ameliorated pathology in the collagen-induced arthritis (CIA) model. However there is evidence implicating a role for other members of the IL-17 cytokine in CIA, including IL-17F, which is closely related to IL-17A. Therefore it is imperative to explore whether blocking the signaling by all members of this cytokine family could be a therapeutic strategy. The CIKS adaptor protein is essential to signaling by IL-17 cytokines. To test whether this adaptor might be a useful therapeutic target, we generated mice lacking CIKS and subjected them to collagen-induced arthritis. We discovered that these mice are totally protected from CIA. This result provides a proof-of-principle indicating that CIKS is a possible target for therapeutic intervention in rheumatoid arthritis. Importantly we also were able to demonstrate that the absence of CIKS mediated signaling also significantly depressed antibody production to collagen, suggesting that IL-17 cytokines may have a previously unsuspected role in auto-antibody production.
NIH ExPorter
NIH ExPorter