类浆细胞性树突状细胞在过敏性哮喘中的作用及皮质激素吸入治疗的作用
2013/04/19
摘要
背景:类浆细胞型树突状细胞(pDC)能浸润急性Th2主导的炎症部位,但其在过敏性哮喘中的作用尚不清楚。
目的:本试验研究过敏原季节外过敏性哮喘患者循环pDCs的特征。
方法:采用流式细胞仪对20名过敏性哮喘患者和18名健康对照者血液中的粘附分子、共刺激分子、免疫球蛋白受体和趋化因子受体进行定量检测。此外,在采用TLR7和TLR9配体刺激pDCs后,检测IL-6、TNF-α和IFN-α分泌。
结果:过敏性哮喘患者的类浆细胞性树突状细胞中,参与炎症组织归巢的趋化因子受体表达增加,包括CCR2、CCR4、CCR9、CCR10、CXCR2、CXCR5和CXCR6,但淋巴结归巢受体CXCR3表达下调。此外,这些pDCs同时存在活化标志物和Th2相关分子(CD40、CD62L、CD64和FcεRIα)表达增加。相反,哮喘患者pDCs中,TLR-7介导的IL-6、TNF-α和IFN-α分泌显著下降。过敏原季节之前,仅皮质激素吸入治疗(ICS)的患者,TLR-9介导的细胞因子反应受到抑制。CD54和OX40L表达观察到类似的表现。
结论:过敏性哮喘患者的活化标志物、Th2相关分子表达增加,循环pDCs的移动潜力增加。这些变化伴随着TLR7介导的细胞因子反应。ICS治疗对循环pDC的特征存在长期影响。
(林江涛 审校)
Clin Exp Allergy. 2013 Mar;43(3):312-21. doi: 10.1111/cea.12064.
Plasmacytoid dendritic cells in allergic asthma and the role of inhaled corticosteroid treatment.
Bratke K, Prieschenk C, Garbe K, Kuepper M, Lommatzsch M, Virchow JC.
Source
Department of Pneumology, University of Rostock, Rostock, Germany.
Abstract
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-α- and IFN-α-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 FcεRIα. In contrast, TLR7-mediated IL-6-, TNF-α- and IFN-α-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.
Clin Exp Allergy. 2013 Mar;43(3):312-21. doi: 10.1111/cea.12064.