Platelet-activating factor induces Th17 cell differentiation.

Platelet-activating factor induces Th17 cell differentiation.
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DOI:
10.1155/2011/913802
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发表时间:
2011
影响因子:
4.6
通讯作者:
Rola-Pleszczynski M
Rola-Pleszczynski M
中科院分区:
医学3区
文献类型:
--
作者:
Drolet AM;Thivierge M;Turcotte S;Hanna D;Maynard B;Stankovà J;Rola-Pleszczynski M

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Th17细胞与许多炎症性和自身免疫性疾病有关。在炎性病变中发现磷脂介质血小板激活因子(PAF)浓度升高,并已被证明能诱导IL-6的产生。我们研究了PAF是否会影响Th17细胞的发育。皮摩尔浓度的PAF可诱导单核细胞来源的朗格汉斯细胞和角质形成细胞表达IL-23、IL-6和IL-1β。此外,当LC经PAF处理后,再与抗CD3和抗CD28激活的T细胞共同培养,后者出现Th17表型,转录调节因子RoRγt的表达显著增加,IL-17、IL-21和IL-22的表达增强。PAF受体拮抗剂WEB2086以及中和IL-23和IL-6R抗体可阻止PAF诱导的Th17的形成。这可能构成了一种以前未知的刺激,促进了炎症过程的发展和持续,这可能是药物干预的结果。
Th17 cells have been implicated in a number of inflammatory and autoimmune diseases. The phospholipid mediator platelet-activating factor (PAF) is found in increased concentrations in inflammatory lesions and has been shown to induce IL-6 production. We investigated whether PAF could affect the development of Th17 cells. Picomolar concentrations of PAF induced IL-23, IL-6, and IL-1β expression in monocyte-derived Langerhans cells (LCs) and in keratinocytes. Moreover, when LC were pretreated with PAF and then cocultured with anti-CD3- and anti-CD28-activated T cells, the latter developed a Th17 phenotype, with a significant increase in the expression of the transcriptional regulator RORγt and enhanced expression of IL-17, IL-21, and IL-22. PAF-induced Th17 development was prevented by the PAF receptor antagonist WEB2086 and by neutralizing antibodies to IL-23 and IL-6R. This may constitute a previously unknown stimulus for the development and persistence of inflammatory processes that could be amenable to pharmacologic intervention.
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