Characterization and Recruitment of Plasmacytoid Dendritic Cells in Synovial Fluid and Tissue of Patients with Chronic Inflammatory Arthritis

Abstract

Dendritic cells (DCs) are thought to play a key role in driving the immunopathogenic response underlying chronic inflammatory arthritis. In this study, we have examined the presence and phenotype of plasmacytoid DCs (pDCs) in the synovial fluids (SF) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PA), and osteoarthritis (OA) and determined the chemotactic properties of SF from these patients toward pDCs. Flow cytometry analysis showed that the percentage of pDCs, identified as a population of Lin−CD123++ cells, is 4- to 5-fold higher in RA SF and PA SF than in OA SF. The morphological and immunophenotypic characterization of pDCs isolated from PA and RA SF indicates that they are in an immature state, most likely due to inhibitory factors present in RA SF, but are still able to undergo maturation when exposed ex vivo to viral agent or unmethylated DNA. CD123+ and BDCA2+ pDCs were detected by immunohistochemistry in RA synovial tissue in which expression of the IFN-α-inducible protein MxA was also found, suggesting production of type I IFN by maturing pDCs. We also show that CXCR3 and CXCR4 are expressed by both blood-derived pDCs and pDCs isolated from RA and PA SF and that CXCL-10, CXCL-11, and CXCL-12 present in RA and PA SF stimulate chemotaxis of blood-derived pDCs. Altogether, these findings suggest that chemokine-driven recruitment of pDCs from the blood to the inflamed synovium could be important in the regulation of the immune response in chronic inflammatory arthritis.

Endogenous HLA–DR–restricted presentation of the cartilage antigens human cartilage gp‐39 and melanoma inhibitory activity in the inflamed rheumatoid joint

“…A previous study, in which ST was immunohistochemically double-stained with mAb 12A and antiCD1a, also demonstrated that the HC gp-39-presenting cells were DC-like cells (6). Moreover, the presence of DCs in the SF of RA patients has been described (35,36).…”

Trafficking properties of plasmacytoid dendritic cells in health and disease

“…lupus erythematosus disease, psoriasis and rheumatoid arthritis) [1,51,52], allergic diseases (i.e. contact dermatitis and nasal mucosa polyps) [53] and in tumors [2,54] (Table 1).…”

The type I interferon system in systemic lupus erythematosus

“…Thus, infiltration of NIPCs/PDCs and expression of IFN␤ and the type I IFN-inducible protein MxA can be detected in the synovia of patients with rheumatoid arthritis (99)(100)(101). Patients with dermatomyositis have a typical IFN gene signature and IFN␣-containing BDCA-2-positive cells in muscle tissue (102,103).…”