Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
Mediators Inflamm. 2011;2011:913802. doi: 10.1155/2011/913802. Epub 2011 Oct 13.
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.
Th17 细胞与许多炎症和自身免疫性疾病有关。血小板激活因子（PAF）是一种脂类介质，在炎症病变中浓度增加，并已被证明可诱导 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 可诱导单核细胞衍生的朗格汉斯细胞（LC）和角质形成细胞中 IL-23、IL-6 和 IL-1β 的表达。此外，当 LC 用 PAF 预处理然后与抗 CD3 和抗 CD28 激活的 T 细胞共培养时，后者发育出 Th17 表型，转录调节剂 RORγt 的表达显著增加，并且增强了 IL-17、IL-21 和 IL-22 的表达。PAF 诱导的 Th17 发育可被 PAF 受体拮抗剂 WEB2086 和中和抗体 IL-23 和 IL-6R 阻断。这可能构成炎症过程发展和持续的先前未知刺激，可能适用于药物干预。
