Important Role of CD11c+ Cells in Inflammatory Arthritis

Antonia Puchner¹, Elisabeth Simader ¹, Victoria Saferding ², Gerhard Kroenke ³, Rene Pfeifle ⁴, Daniel Aletaha ¹, Josef Smolen ¹ and Stephan Blueml ¹, ¹Medical University of Vienna, Vienna, Austria, ²Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, ³Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nuremberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Austria, ⁴University Hospital Erlangen, Erlangen, Germany

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Arthritis, Dendritic cells, mouse model and cd11c, osteoclasts

Session Information

Date: Monday, November 11, 2019

Title: RA – Animal Models Poster

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: 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.

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.

Conclusion: 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.

Disclosure: A. Puchner, None; E. Simader, None; V. Saferding, None; G. Kroenke, None; R. Pfeifle, None; D. Aletaha, AbbVie, 2, 5, 8, AbbVie, Janssen, Lilly, Novartis, Pfizer, and Roche, 5, AbbVie, Merck Sharp and Dohme, and Roche., 2, Amgen, 5, 8, Bristol-Myers Squibb, 8, Bristol-Myers Squibb, Celgene, Merck Sharp and Dohme, and UCB, 8, Celgene, 5, 8, Janssen, 5, Lilly, 5, 8, Medac, 5, 8, Merck, 5, 8, Merck Sharp and Dohme, 2, 8, Novartis, 2, 5, 8, Pfizer, 5, 8, Roche, 2, 5, 8, Sandoz, 5, 8, Sanofi/Genzyme, 5, 8, UCB, 8; J. Smolen, AbbVie, Amgen, Astra-Zeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, 8, AbbVie, Eli Lilly, Janssen, MSD, Pfizer, Roche, 2, ILTOO, Janssen, Medimmune, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB, 8; S. Blueml, None.

To cite this abstract in AMA style:

Puchner A, Simader E, Saferding V, Kroenke G, Pfeifle R, Aletaha D, Smolen J, Blueml S. Important Role of CD11c+ Cells in Inflammatory Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/important-role-of-cd11c-cells-in-inflammatory-arthritis/. Accessed .

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