Rheumatoid arthritis synovium contains plasmacytoid dendritic cells.

Rheumatoid arthritis synovium contains plasmacytoid dendritic cells.
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DOI:
10.1186/ar1467
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发表时间:
2005
影响因子:
4.9
通讯作者:
Thomas R
Thomas R
中科院分区:
医学2区
文献类型:
--
作者:
Cavanagh LL;Boyce A;Smith L;Padmanabha J;Filgueira L;Pietschmann P;Thomas R

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我们之前已经描述了在类风湿关节炎(RA)滑膜中抗原呈递HLA-DR+核RelB+树突状细胞(DCs)的富集。CD123+HLA-DR+浆细胞样dc (pDCs)及其前体已在人外周血(PB)、淋巴组织和一些炎症组织中发现。我们假设pDCs被募集到炎症的RA滑膜环境中,并在RA中作为抗原呈递细胞(APCs)和炎症细胞发挥作用。通过流式细胞术、免疫组织化学和电镜比较CD11c+髓系dc和CD123+ pDCs在正常和RA的PB、滑液(SF)和滑液组织中的差异,并进行分类进行功能研究。核性RelB-CD123+ dc位于RA的血管周围区域,与核性RelB+CD123- dc的频率相似,但与正常滑膜组织下层不同。除了HLA-DR的高表达外,SF - pDCs的数量和表型与正常PB - pDCs相似。虽然PB - pDCs的APC功能不如PB -髓系dc有效,但RA - SF - pDCs有效激活静息异体PB - T细胞,并在同种异体T细胞与两种类型的SF - dc孵育后产生高水平的IFN-γ、IL-10和肿瘤坏死因子α。因此,pDCs被募集到RA滑膜组织,并组成一个APC群体,不同于先前描述的核RelB+滑膜dc。pDCs可能对局部炎症环境有重要影响。
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.
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