title: Rheumatoid arthritis synovium contains plasmacytoid dendritic cells.
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-gamma, IL-10, and tumor necrosis factor alpha 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.
authors.affiliation: Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Lois L
authors.initials: LL
authors.lastname: Cavanagh
authors.forename: Amanda
authors.initials: A
authors.lastname: Boyce
authors.forename: Louise
authors.initials: L
authors.lastname: Smith
authors.forename: Jagadish
authors.initials: J
authors.lastname: Padmanabha
authors.forename: Luis
authors.initials: L
authors.lastname: Filgueira
authors.forename: Peter
authors.initials: P
authors.lastname: Pietschmann
authors.forename: Ranjeny
authors.initials: R
authors.lastname: Thomas
mesh_terms: D017951:Antigen Presentation; D015535:Arthritis, Psoriatic / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D039521:CD11c Antigen / Q000032:analysis; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D053650:Interleukin-3 Receptor alpha Subunit; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D016185:Receptors, Interleukin-3 / Q000032:analysis; D013167:Spondylitis, Ankylosing / Q000473:pathology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D051841:Transcription Factor RelB / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; C497593:RELB protein, human; D016185:Receptors, Interleukin-3; D014409:Tumor Necrosis Factor-alpha; D051841:Transcription Factor RelB
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