Rheumatoid Arthritis Synovium Contains Two Subsets of CD83− DC-LAMP− Dendritic Cells with Distinct Cytokine Profiles

Dendritic cells (DCs) have been proposed to play a pivotal role in the initiation and perpetuation of rheumatoid arthritis (RA) by presentation of arthritogenic antigens to T cells. We investigated the in vivo characteristics of two major DC subsets, myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), in RA synovial tissue (ST) by measuring their frequency, phenotype, distribution, and cytokine expression. ST was obtained by arthroscopy from 20 RA, 8 psoriatic arthritis, and 10 inflammatory osteoarthritis patients. Levels of CD1c+ mDCs and CD304+ pDCs present in ST were quantified by digital image analysis, and their distribution was assessed by double immunolabeling with antibodies against CD3 and CD8. The maturation status and cytokine profile of mDCs and pDCs were quantified by double-immunofluorescence microscopy. In RA patients, the number of CD304+ pDCs exceeded that of CD1c+ mDCs, with the majority of infiltrating DCs being CD83− or DC-LAMP− . Synovial pDC numbers were especially increased in RA patients who were positive for rheumatoid factor and anti-citrullinated peptide antibody. mDCs and pDCs were localized adjacent to lymphocyte aggregates. In ST from RA patients, both mDCs and pDCs expressed interleukin (IL)-15. IL-18 and interferon (IFN)-α/β were mainly expressed by pDCs whereas IL-12p70 and IL-23p19 expression was predominant in mDCs. These data characterize the phenotypes of mDCs and pDCs in inflammatory synovitis and define for the first time the cytokine expression profile of these DC subsets.