Distribution of regulatory T cells and interaction with dendritic cells in the synovium of rheumatoid arthritis

Objectives: The aim of this study was to investigate the tissue distribution of regulatory T cells (Treg cells) and their interaction with dendritic cells (DCs) in synovium from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Methods: Immunohistochemical staining was used to investigate the distribution of Treg cells and the interaction between Treg cells and DCs in RA (n = 30) and OA synovium (n = 8). mRNA levels were measured by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results: Large numbers of Treg cells were observed in lymphoid aggregates and perivenular infiltration areas in the RA synovium. Specific cellular markers for Treg cells (Foxp3, CD39, LAG-3, and Nrp-1) were found in lymphoid aggregates, perivenular infiltration, and scattered in lining layer areas. As molecular markers for DCs, DC-LAMP, DEC-205, CD80/86, and CD83 were also detected in the lymphoid aggregates and perivenular infiltration areas in RA. Furthermore, the co-localization of Treg cells and DCs was confined mainly in the lymphoid aggregation areas. The number of DCs increased significantly more than the number of Treg cells with inflammatory progression in RA. mRNA expression of the cellular markers for Treg cells (Foxp3, LAG-3, and Nrp-1) and the molecular markers for DCs (DC-LAMP and DEC-205) was increased in RA compared with OA synovium. Conclusions: Our results indicate that DCs play a dominant role in regulating the activation and progression of immune responses in RA, even though the number of Treg cells was upregulated at the same time. This suggests that Treg cells do not function normally to suppress the maturation of DCs in the RA synovium.