P122 Important role of dendritic cells in inflammatory arthritis

Career situation of first and presenting author Student for a master or a PhD. Introduction Important role of dendritic cells in inflammatory arthritis. Objectives Investigation of the role of CD11c + cells in joint inflammation and destruction. Methods We analyzed histological sections of K/BxN serum transfer arthritis as well as hTNFtg arthritis for the presence of CD11c + cells by immunohistochemistry. We used CD11c-diphteria toxin receptor (DTR) transgenic mice. K/BxN serum transfer arthritis was induced, and mice were given either DT or PBS or in wt and BARF3 deficient mice. In addition CD11c DTR mice were crossed into hTNFtg animals and also received either DT or PBS. The severity of arthritis was determined clinically and histologically. Results Both CD8 + CD11c + and CD11b + CD11c + , can be found in synovial tissue in TNF driven arthritis. Upon depletion of CD11c + cells clinical signs of K/BxN serum transfer arthritis were significantly reduced. Histological analysis found reduced synovial inflammation after the depletion of CD11c + cells in K/BxN arthritis. In addition, local bone destruction and the number of osteoclasts was also significantly reduced. In addition to K/BxN arthritis, we found that also in TNF-driven arthritis depletion of CD11c + cells led to a striking reduction of synovial inflammation and a complete depletion of osteoclasts. Conclusions These data show that in addition to initiating an adaptive immune response, CD11c + dendritic cells, are also involved in innate effector mechanisms of inflammatory arthritis. Especially CD11b + CD11c + and monocyte derived inflammatory seem to play a role in inflammatory arthritis, suggesting that they could be an important therapeutic target. References Sarkar S, Fox DA. Dendritic cells in rheumatoid arthritis. Front Biosci . 2005;10:656–65. Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 31:563–604. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392(6673):245–52. Acknowledgements We would like to thank the Medical University of Vienna and especially Prof. Smolen for their support and all members of the University of Erlangen for their assistance. Disclosure of Interest None declared.