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Plasmacytoid dendritic cells in allergic asthma and the role of inhaled corticosteroid treatment

机译：浆细胞样树突状细胞在过敏性哮喘中的作用及吸入糖皮质激素的治疗​​作用

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Background: Plasmacytoid dendritic cells (pDCs) infiltrate sites of acute Th2-dominant inflammation, but their role in allergic asthma remains unclear. Objective: To characterize circulating pDCs from patients with allergic asthma outside their respective allergen season. Methods: Adhesion molecules, co-stimulatory molecules, immunoglobulin receptors and chemokine receptors were quantified on blood pDCs from 20 patients with allergic asthma and 18 healthy controls using flow cytometry. In addition, IL-6-, TNF-??- and IFN-??-secretion were analysed after stimulating isolated pDCs with TLR7- and TLR9-ligands. Results: Plasmacytoid dendritic cells from patients with allergic asthma showed an increased expression of chemokine receptors involved in inflamed tissue homing such as CCR2, CCR4, CCR9, CCR10, CXCR2, CXCR5 and CXCR6, while the expression of the lymph node homing receptor CXCR3 was down-regulated. In addition, these pDCs exhibited a higher expression of activation markers and Th2-associated molecules such as CD40, CD62L, CD64 and Fc??RI??. In contrast, TLR7-mediated IL-6-, TNF-??- and IFN-??-secretion was significantly reduced in pDCs from patients with asthma. The TLR9-mediated cytokine response was only suppressed in those patients who were treated with inhaled corticosteroids (ICS) during previous allergen seasons. The same effect was observed for CD54 and OX40L expression. Conclusions: We report an increased expression of activation markers, and Th2-associated molecules, and an increased migratory potential of circulating pDCs in allergic asthma. These changes are accompanied by a reduced TLR7-mediated cytokine response. In addition, our results suggest a longterm impact of ICS treatment on the characteristics of circulating pDCs. ? 2012 Blackwell Publishing Ltd.
机译：背景：浆细胞样树突状细胞（pDC）渗透到急性Th2占主导地位的炎症部位，但它们在过敏性哮喘中的作用仍不清楚。目的：鉴定过敏原季节以外的过敏性哮喘患者的循环pDC。方法：采用流式细胞术对20例过敏性哮喘患者和18例健康对照者的血液pDC上的黏附分子，共刺激分子，免疫球蛋白受体和趋化因子受体进行定量。另外，在用TLR7-和TLR9-配体刺激分离的pDC后，分析了IL-6-，TNF-α-和IFN-γ-分泌。结果：过敏性哮喘患者的浆细胞样树突状细胞显示参与炎症组织归巢的趋化因子受体（如CCR2，CCR4，CCR9，CCR10，CXCR2，CXCR5和CXCR6）的表达增加，而淋巴结归巢受体CXCR3的表达下降-调节。另外，这些pDC显示出较高的活化标记和与Th2相关的分子如CD40，CD62L，CD64和FcγRIRI的表达。相反，哮喘患者的pDCs中TLR7介导的IL-6-，TNF-α-和IFN-β-分泌显着降低。 TLR9介导的细胞因子反应仅在以前的过敏原季节中接受过吸入皮质类固醇（ICS）治疗的患者中得到抑制。对于CD54和OX40L表达观察到相同的效果。结论：我们报道了过敏性哮喘中激活标记物和Th2相关分子的表达增加，循环中的pDCs的迁移潜力增加。这些变化伴随着TLR7介导的细胞因子反应减少。此外，我们的结果表明ICS治疗对循环pDCs特征的长期影响。 ？ 2012布莱克威尔出版有限公司

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