A2.5 CD11c+ Dendritic Cells Play an Important Proinflammatory Role in Inflammatory Arthritis

Abstract

<h3>Backround</h3> Dendritic cells (DCs) play an important role in bridging the innate and the adaptive immune response by serving as antigen presenting cells and are therefore implicated in the initiation of chronic autoimmune diseases, including rheumatoid arthritis. Using the K/BxN serum transfer arthritis, a model of human rheumatoid arthritis, which depends only on the innate immune system, allowed us to investigate the innate role role of dendritic cells in inflammatory arthritis. <h3>Methods</h3> KBxN serum transfer arthritis was induced in CD11c-diphteria toxin receptor (DTR) transgenic mice, which express the human diphtheria-toxin receptor under the CD11c promoter. This allows for specific depletion of CD11c+ cells by administration of diphtheria toxin (DT). DT or PBS were given on day -1, 3, 6 and 9 and the severity of arthritis was determined clinically and histologically. In addition, serum transfer arthritis was induced in wild type animals who also received DT. <h3>Results</h3> Efficient depletion of DCs from the spleen after injection of DT was confirmed by flow cytometry and histological analysis. Clinical scores of arthritis showed that CD11c-DTR transgenic mice had significantly reduced paw swelling and loss of grip strength compared to PBS treated animals. In contrast, wild type animals receiving DT showed identical clinical signs of arthritis as PBS treated animals, excluding unspecific effects of DT in mice. Histological analysis found that CD11c-DTR transgenic mice that had received DT displayed decreased synovial inflammation and a trend towards reduced local bone destruction. <h3>Conclusions</h3> These data show that dendritic cells are involved in innate reactions leading to inflammatory arthritis and suggest that dendritic cells could be an important target for rheumatoid arthritis therapy.