Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Clin Exp Allergy. 2012 Dec;42(12):1756-64. doi: 10.1111/j.1365-2222.2012.04060.x.
Differentiation and activation of CD4(+) T cells is controlled by various cytokines produced by innate immune cells. We have shown that eosinophils (EOS) have the potential to influence Th1 and Th2 cytokine generation by CD4(+) cells, but their influence on IL-17A (IL-17) has not been established.
The purpose of this study is to determine the effect of EOS on IL-17 production by lymphocytes.
Pre-activated CD4(+) T cells were cultured in the presence of either autologous EOS or EOS culture supernatants. Expression of IL-17 was determined by real-time quantitative PCR (qPCR) after 5 h and protein level was measured after 48 h. To determine the effect of allergen-induced airway EOS on IL-17, subjects with mild allergic asthma underwent bronchoscopic segmental bronchoprovocation with allergen (SBP-Ag) after a treatment with an anti-IL-5 neutralizing antibody (mepolizumab) to reduce airway eosinophilia. IL-17 mRNA was measured in bronchoalveolar lavage (BAL) cells by qPCR.
In vitro, EOS significantly increased IL-17 production by CD4(+) T cells. Addition of exogenous IL-1ß increased expression of IL-17 mRNA by CD4(+) T cells. EOS expressed and released IL-1ß. Furthermore, levels of IL-1ß in EOS supernatants highly correlated with their ability to increase IL-17 expression by CD4(+) T cells, and neutralizing antibody to IL-1ß reduced expression of IL-17 mRNA. In vivo, reduction of EOS in the airway using mepolizumab was associated with diminished IL-17 expression after SBP-Ag.
Our data demonstrate that EOS can promote IL-17 production through the release of IL-1ß. Enhanced IL-17 cytokine production is another mechanism by which EOS may participate in pathogenesis of allergic airway inflammation in asthma.
CD4(+) T 细胞的分化和激活受固有免疫细胞产生的各种细胞因子控制。我们已经表明，嗜酸性粒细胞（EOS）有可能影响 CD4(+)细胞产生 Th1 和 Th2 细胞因子，但它们对白细胞介素-17A（IL-17）的影响尚未确定。
本研究旨在确定 EOS 对淋巴细胞产生 IL-17 的影响。
将预激活的 CD4(+) T 细胞在自体 EOS 或 EOS 培养上清液中培养。5 h 后通过实时定量 PCR（qPCR）测定 IL-17 的表达，48 h 后测定蛋白水平。为了确定过敏原诱导的气道 EOS 对 IL-17 的影响，轻度过敏性哮喘患者在接受抗白细胞介素-5 中和抗体（mepolizumab）治疗以减少气道嗜酸性粒细胞增多后，进行过敏原诱导的支气管节段支气管激发（SBP-Ag）。通过 qPCR 测量支气管肺泡灌洗液（BAL）细胞中的 IL-17 mRNA。
在体外，EOS 显著增加 CD4(+) T 细胞产生的 IL-17。添加外源性 IL-1ß 增加了 CD4(+) T 细胞中 IL-17 mRNA 的表达。EOS 表达并释放 IL-1ß。此外，EOS 上清液中 IL-1ß 的水平与其增加 CD4(+) T 细胞中 IL-17 表达的能力高度相关，中和抗体抑制 IL-1ß 降低了 IL-17 mRNA 的表达。在体内，使用 mepolizumab 减少气道中的 EOS 与 SBP-Ag 后 IL-17 表达减少相关。
我们的数据表明，EOS 可以通过释放 IL-1ß 促进 IL-17 的产生。增强的 IL-17 细胞因子产生是 EOS 可能参与哮喘过敏气道炎症发病机制的另一种机制。
