Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment
Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment
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DOI：
10.1182/blood-2004-01-0041
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发表时间：
2004-12-15
期刊：
影响因子：
20.3
通讯作者：
Servet-Delprat, C
中科院分区：
文献类型：
--
作者：
Rivollier, A;Mazzorana, M;Servet-Delprat, C
树突状细胞（Dendritic cells，DC）是启动免疫应答的单核细胞，破骨细胞是多核骨吸收细胞，它们来源于单核细胞/巨噬细胞前体细胞。粒细胞-巨噬细胞集落刺激因子和巨噬细胞集落刺激因子（M-CSF）可调节小鼠两种谱系的分化。使用人单核细胞衍生的DC在体外产生的，我们表明，未成熟的DC转分化成功能性破骨细胞（OC）的存在下，M-CSF和核因子-κ B受体激活剂配体（RANKL）。转分化通过表达CD 14、CD 1a和RANKL并能够诱导RANKL（+）T细胞增殖的中间贴壁双极梭形单核细胞的融合来进行。令人惊讶的是，体外DC融合比单核细胞融合更快且更有效地形成多核巨细胞。本文报道的转分化过程支持分化的髓系吞噬细胞内存在高细胞可塑性。重要的是，这一过程被类风湿性关节炎滑液大大增强，并涉及促炎细胞因子，如白细胞介素1或肿瘤坏死因子a，以及细胞外基质的组分，如透明质酸。因此，我们的数据表明，DC衍生的OC可能直接参与溶骨性病变中观察到的人类炎症性骨疾病，如类风湿性关节炎或在特定形式的朗格汉斯细胞组织细胞增生症，其特征在于积累的未成熟的皮肤DC和慢性溶骨性病变。(C)2004年，美国血液学会。
Dendritic cells (DCs), the mononuclear cells that initiate immune response, and osteoclasts, the multinucleated bone-resorbing cells, are derived from monocyte/macrophage precursor cells. Granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor (M-CSF) reciprocally regulate the differentiation of both lineages in mice. Using human monocyte-derived DCs generated in vitro, we show that immature DCs transdifferentiate into functional osteoclasts (OCs) in the presence of M-CSF and receptor activator of nuclear factor-kappaB ligand (RANKL). Transdifferentiation operates through fusion of intermediate adherent bipolar fusiform mononuclear cells expressing CD14, CD1a, and RANKL and able to induce RANKL(+) T-cell proliferation. Surprisingly, DC fusion in vitro is faster and more efficient than monocyte fusion to form multinucleated giant cells. The transdifferentiation process reported here supports the existence of a high cellular plasticity within differentiated myeloid phagocytes. Importantly, this process is greatly enhanced by rheumatoid arthritis synovial fluid and involves proinflammatory cytokines such as interleukin 1 or tumor necrosis factor a, as well as components of the extracellular matrix such as hyaluronic acid. Our data therefore suggest that DC-derived OCs may be directly involved in the osteolytic lesions observed in human inflammatory bone diseases such as rheumatoid arthritis or in particular forms of Langerhans cell histiocytosis, characterized by accumulation of immature skin DCs and chronic lytic bone lesions. (C) 2004 by The American Society of Hematology.