Objectives: To characterize the phenotype of the putative dendritic cells strongly expressing Jak3 and STAT4, which have been previously identified in the synovial tissue of patients with active Rheumatoid Arthritis (RA).
Methods: Synovial biopsy specimens were obtained at arthroscopy from 30 patients with active RA (42 synovial biopsies). Immunohistological analysis was performed using monoclonal antibodies (Mab) to detect dendritic cell subsets including activation markers as well cytokines relevant to dendritic cell function. Co- localisation of cell surface markers and cytokines was assessed primarily using sequential sections, with results confirmed by dual immunohistochemistry and immunofluorescence with confocal microscopy.
Results:The dendritic cells identified in RA synovial tissue which strongly express Jak3 also strongly express STAT4 and STAT 6 and are correlated with the presence of rheumatoid factor. These cells are not confined to a single dendritic cell subset, with cells having phenotypes consistent with both myeloid and plasmacytoid type of dendritic cells. The activation status of these dendritic cells suggests that they are maturing or mature dendritic cells. These dendritic cells produce IL-12 as well as Interferon á and ã.
Conclusions:The close correlation of these dendritic cells with the presence of rheumatoid factor, a prognostic factor for worse disease outcomes and the strong expression by these cells of components of the Jak/STAT transcription factor pathway suggest a potential therapeutic target for the treatment of RA.
- myeloid dendritic cells
- plasmacytoid dendritic cells
- rheumatoid arthritis