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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells.
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Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells.

机译：病毒刺激的浆细胞样树突状细胞产生趋化因子并诱导T细胞和NK细胞迁移。

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The natural interferon (IFN)-producing cell is now known to be identical to the plasmacytoid dendritic cell (PDC). These are Lin-, CD123+, CD11c-, and human leukocyte antigen-DR+ cells that secrete large amounts of IFN-alpha (1-2 IU/cell) when stimulated by enveloped viruses such as herpes simplex virus. In the current study, we have evaluated chemokine expression by virally stimulated PDC. Up-regulation of mRNA for CCL4, CCL3, CCL5, CCL2, and CXC chemokine ligand (CXCL)10 in herpes simplex virus-stimulated PDC was detected by RNAse protection assays. In contrast, PDC-depleted peripheral blood mononuclear cells did not up-regulate these mRNA species upon viral stimulation. Enzyme-linked immunosorbent assay and/or intracellular flow cytometry confirmed production of these proteins, and studies indicated overlapping production of IFN-alpha and the other cytokines/chemokines by PDC. Endocytosis plays a critical role in chemokine induction, as disruption of the pathway inhibits the response. However, transcription of viral genes is not required for chemokine induction. Autocrine IFN-alpha signaling in the PDC could account for a portion of the CXCL10 and CCL2 production in virally stimulated PDC but was not responsible for the induction of the other chemokines. To evaluate the functional role of the chemokines, chemotaxis assays were performed using supernatants from virally stimulated PDC. Activated T cells and natural killer cells, but not naive T cells, were preferentially recruited by these PDC supernatants. Migration was subsequently inhibited by addition of neutralizing antibody to CCL4 and CXCL10. We hypothesize that virally induced chemokine production plays a pivotal role in the homing of leukocytes to PDC.
机译：现在已知天然干扰素（IFN）产生细胞与浆细胞样树突细胞（PDC）相同。它们是Lin-，CD123 +，CD11c-和人白细胞抗原-DR +细胞，在被包膜病毒（例如单纯疱疹病毒）刺激时会分泌大量IFN-α（1-2 IU /细胞）。在当前的研究中，我们通过病毒刺激的PDC评估了趋化因子的表达。通过RNA酶保护试验检测到单纯疱疹病毒刺激的PDC中CCL4，CCL3，CCL5，CCL2和CXC趋化因子配体（CXCL）10的mRNA上调。相反，PDC耗尽的外周血单核细胞在病毒刺激后并未上调这些mRNA种类。酶联免疫吸附测定和/或细胞内流式细胞术证实了这些蛋白质的产生，并且研究表明PDC重叠产生了IFN-α和其他细胞因子/趋化因子。内吞作用在趋化因子诱导中起关键作用，因为该途径的破坏抑制了反应。然而，诱导趋化因子不需要病毒基因的转录。 PDC中的自分泌IFN-α信号传导可能占病毒刺激的PDC中CXCL10和CCL2产生的一部分，但不负责诱导其他趋化因子。为了评估趋化因子的功能作用，使用来自病毒刺激的PDC的上清液进行趋化性测定。这些PDC上清液优先募集活化的T细胞和天然杀伤细胞，而非天然T细胞。随后通过向CCL4和CXCL10添加中和抗体来抑制迁移。我们假设病毒诱导的趋化因子生产在白细胞归巢到PDC中起关键作用。

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