SAT0061 IMPORTANT ROLE OF CD11C+ CELLSIN INFLAMMATORY ARTHRITIS
Authors: Antonia Puchner, Elisabeth Simader, Victoria Saferding, Gerhard Krönke, Rene Pfeifle, Daniel Aletaha, Josef S. Smolen, Stephan Blüml
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Dendritic cells (DCs) are important antigen presenting cells (APCs) and therefore they play an important role in bridging the innate and the adaptive immune response. DCs can be divided in different subsets with specific functions. As powerful APCs, DCs are thought to play an important role in the induction of autoimmune diseases such as rheumatoid arthritis. However, the active role of DCs in joint inflammation is not known yet. <h3>Objectives:</h3> Investigation of the role of DCs cells in joint inflammation and destruction. <h3>Methods:</h3> 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. <h3>Results:</h3> 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. <h3>Conclusion:</h3> 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. <h3>Disclosure of Interests:</h3> Antonia Puchner: None declared, Elisabeth Simader: None declared, Victoria Saferding: None declared, Gerhard Krönke Grant/research support from: Lilly, Pfizer, Speakers bureau: Novartis, Rene Pfeifle: None declared, Daniel Aletaha Grant/research support from: AbbVie, Bristol-Myers Squibb, and MSD, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Medac, Merck, MSD, Pfizer Inc, Roche, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Medac, Merck, MSD, Pfizer Inc, Roche, and UCB, Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, MSD, Pfizer, Roche, Consultant for: AbbVie, Amgen, Astra-Zeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, MedImmune, MSD, Novartis, Pfizer, Roche, Samsun, Sanofi, UDB, Speakers bureau: AbbVie, Amgen, Astra-Zeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, MedImmune, MSD, Novartis, Pfizer, Roche, Samsun, Sanofi, UDB, Stephan Blüml: None declared