Session Title: Innate Immunity and Rheumatic Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: Dendritic cells (DCs) play an important role in bridging innate and adaptive immune responses by serving as antigen presenting cells. Therefore DCs are 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 of dendritic cells in inflammatory arthritis.
Methods: 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 was 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.
Results: Efficient depletion of DCs after injection of DT was confirmed by flow cytometry and histological analysis of spleens of CD11c-DTR transgenic mice. Clinical scores of arthritis showed that CD11c-DTR transgenic mice had significantly reduced paw swelling and loss of grip strength after administration of DT when compared to PBS treated animals. Moreover, histological analysis showed decreased synovial inflammation and a trend towards reduced local bone destruction in these animals. In contrast, in wild type mice receiving DT we detected identical clinical signs of arthritis as in PBS treated animals, indicating that DT has no unspecific effects on the development of arthritis.
Conclusion: These data show that DCs are involved in innate reactions leading to inflammatory arthritis and therefore could be an important target for treating rheumatoid arthritis.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cd11c-dendritic-cells-play-an-important-proinflammatory-role-in-inflammatory-arthritis/