Abstract
We have previously described enrichment of antigen-presenting HLA-DR+ nuclear RelB+ dendritic cells (DCs) in rheumatoid arthritis (RA) synovium. CD123+HLA-DR+ plasmacytoid DCs (pDCs) and their precursors have been identified in human peripheral blood (PB), lymphoid tissue, and some inflamed tissues. We hypothesized recruitment of pDCs into the inflamed RA synovial environment and their contribution as antigen-presenting cells (APCs) and inflammatory cells in RA. CD11c+ myeloid DCs and CD123+ pDCs were compared in normal and RA PB, synovial fluid (SF), and synovial tissue by flow cytometry, immunohistochemistry, and electron microscopy and were sorted for functional studies. Nuclear RelB-CD123+ DCs were located in perivascular regions of RA, in a similar frequency to nuclear RelB+CD123- DCs, but not normal synovial tissue sublining. Apart from higher expression of HLA-DR, the numbers and phenotypes of SF pDCs were similar to those of normal PB pDCs. While the APC function of PB pDCs was less efficient than that of PB myeloid DCs, RA SF pDCs efficiently activated resting allogeneic PB T cells, and high levels of IFN-γ, IL-10, and tumor necrosis factor α were produced in response to incubation of allogeneic T cells with either type of SF DCs. Thus, pDCs are recruited to RA synovial tissue and comprise an APC population distinct from the previously described nuclear RelB+ synovial DCs. pDCs may contribute significantly to the local inflammatory environment.
Highlights
Plasmacytoid dendritic cells are a distinct population of antigen-presenting cells (APCs) with the capacity for potent antigen-presenting function and production of large amounts of cytokines, including tumor necrosis factor (TNF)-α and IFN-α
PDCs are recruited to rheumatoid arthritis (RA) synovial tissue and comprise an APC population distinct from the previously described nuclear RelB+ synovial dendritic cells (DCs). Plasmacytoid dendritic cells (pDCs) may contribute significantly to the local inflammatory environment
CD123+ nuclear RelB- DCs are located in perivascular regions of RA synovial tissue We have previously shown that synovial tissue in RA and spondyloarthropathy is enriched in differentiated myeloid DCs that express CD33, CD11c, MHC class II, costimulatory molecules, and nuclear RelB [21,25]
Summary
Plasmacytoid dendritic cells (pDCs) are a distinct population of antigen-presenting cells (APCs) with the capacity for potent antigen-presenting function and production of large amounts of cytokines, including tumor necrosis factor (TNF)-α and IFN-α. While pDCs were first demonstrated in the T-cell areas of lymph nodes [5,9], precursors of this DC population have been isolated from several sources, including normal peripheral blood (PB), thymus, fetal liver, and bone marrow [10]. They do not reside in normal peripheral tissues, pDCs have been shown to infiltrate certain inflamed tissues and tumor sites, including the skin in psoriasis and lupus, the cerebrospinal fluid in multiple sclerosis, and melanoma and ovarian carcinoma [11,12,13,14,15]. While pDCs play an important effector role in viral disease, being the major producers of IFN-α and having a primary role in innate immunity, there is evidence that they may play an immunoregulatory role, through the induction of Th2 (T helper 2)-type cytokines [9,16,17,18]
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