TLR2-activated human langerhans cells promote Th17 polarization via IL-1β, TGF-β and IL-23
TLR2-activated human langerhans cells promote Th17 polarization via IL-1β, TGF-β and IL-23
复制标题
DOI：
10.1002/eji.200838742
复制
发表时间：
2009-05-01
影响因子：
5.4
通讯作者：
Peiser, Matthias
中科院分区：
文献类型：
--
作者：
Aliahmadi, Ehsan;Gramlich, Robert;Peiser, Matthias
细胞因子IL-6、IL-1 β、TGF-β和IL-23被认为促进Th 17定型。朗格汉斯细胞（LC）代表表皮外皮肤层中的DC，表皮外皮肤层是广泛暴露于病原体攻击的环境。像LC这样的器官驻留DC是否能引起Th 17免疫应答的问题仍然是开放的。我们的结果显示，在细菌激动剂的刺激下，表皮LC和LC样细胞TLR 2依赖性地获得活化Th 17细胞的能力。在Th 17细胞中，检测到类维生素A孤儿受体γ β的表达。为了阐明IL-17（+）细胞本身是否可以通过刺激LC而产生，我们没有通过抑制分化的抗体来抑制Th 1/Th 2驱动途径。在CD 1c（+）/langerin（+）单核细胞衍生的LC样细胞（MoLC）中，巨噬细胞活化脂肽2和肽聚糖（PGN）诱导细胞因子IL-6、IL-1 β和IL-23的释放。发现TGF-β，LC分化和存活所需的细胞因子，组成性分泌。抗TLR 2抑制MoLC分泌IL-6、IL-1 β和IL-23，而TGF-β不受影响。IL-17的量和IL-17与IFN-γ表达的比率在MoLC中比在单核细胞来源的DC共培养的Th细胞中更高。抗IL-1 β、抗TGF-β和抗IL-23降低了Th 17细胞的诱导。有趣的是，阻断PGN刺激的MoLC上的TLR 2阻止Th细胞极化成Th 17细胞。因此，我们的研究结果表明TLR 2在引发炎症皮肤中的Th 17免疫应答中的作用。
The cytokines IL-6, IL-1 beta, TGF-beta, and IL-23 are considered to promote Th17 commitment. Langerhans cells (LC) represent DC in the outer skin layers of the epidermis, an environment extensively exposed to pathogenic attack. The question whether organ-resident DC like LC can evoke Th17 immune response is still open. our results show that upon stimulation by bacterial agonists, epidermal LC and LC-like cells TLR2-dependently acquire the capacity to polarize Th17 cells. In Th17 cells, expression of retinoid orphan receptor gamma beta was detected. To clarify if IL-17(+) cells could arise per se by stimulated LC we did not repress Th1/Th2 driving pathways by antibodies inhibiting differentiation. In CD1c(+)/langerin(+) monocyte-derived LC-like cells (MoLC), macrophage-activating lipopeptide 2, and peptidoglycan (PGN) induced the release of the cytokines IL-6, IL-1 beta, and IL-23. TGF-beta, a cytokine required for LC differentiation and survival, was found to be secreted constitutively. Anti-TLR2 inhibited secretion of IL-6, IL-1 beta, and IL-23 by MoLC, while TGF-beta was unaffected. The amount of IL-17 and the ratio of IL-17 to IFN-gamma expression was higher in MoLC- than in monocyte-derived DC-cocultured Th cells. Anti-IL-1 beta, -TGF-beta and -IL-23 decreased the induction of Th17 cells. Interestingly, blockage of TLR2 on PGN-stimulated MoLC prevented polarization of Th cells into Th17 cells. Thus, our findings indicate a role of TLR2 in eliciting Th17 immune responses in inflamed skin.