Characterization of BDCA1 and BDCA4 dendritic cell subsets in rheumatoid arthritis patients

Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by chronic inflammation of the joints leading to destruction of cartilage and bone. RA is characterized by synovial lining hyperplasia and chronic infiltration by T and B cells, monocyte/macrophages, dendritic cells (DC) and other cells. DC are the only antigen-presenting cells that can prime naïve Th cells and initiate immune responses. In peripheral blood two major DC subsets can be found: BDCA1⁺CD11c⁺CD123low (myeloid), with the ability to produce IL-12; and BDCA4⁺CD11c^-CD123high (plasmacytoid), which produce large amounts of type I interferons (IFN-α/β).

To gain insight into the in vivo characteristics of DC, we investigated the distribution of BDCA1⁺ and BDCA4⁺ DC in RA patients compared with healthy controls and non-RA patients.

The frequencies of BDCA1⁺ and BDCA4⁺ DC in peripheral blood and synovial fluid were analyzed by FACS analysis. Immunohistochemistry was performed in synovial tissue from RA patients to get more insight into the distribution of these two DC subsets in vivo.

We found that the frequencies of both BDCA1⁺ and BDCA4⁺ DC in peripheral blood of RA patients are decreased compared with healthy controls and non-RA patients. Although the frequencies of both DC subsets in synovial fluid from RA patients were increased compared with peripheral blood, they did not differ significantly from non-RA patients. In rheumatoid synovial tissue, both DC subsets were localized close to CD3 and CD8 T cell infiltrates.

BDCA1⁺ and BDCA4⁺ DC are preferentially localized in the synovium of RA patients, where they could stimulate memory T cells and sustain the inflammatory process. Conceivably, immuno-modulation by targeting synovial DC might provide a novel anti-rheumatic strategy.

Affiliations

1. Division of Clinical Immunology/Rheumatology, AMC, UvA, Amsterdam, The Netherlands
   • MC Lebre
   • , SW Tas
   • , P Reinders-Blankert
   • , TJM Smeets
   •  & PP Tak

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