Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma.
Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma.
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DOI：
10.4049/jimmunol.182.3.1404
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发表时间：
2009-02-01
期刊：
影响因子：
--
通讯作者：
Jarjour NN
中科院分区：
文献类型：
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作者：
Kelly EA;Koziol-White CJ;Clay KJ;Liu LY;Bates ME;Bertics PJ;Jarjour NN
IL-7的主要功能是促进T细胞的成熟和存活。通过芯片表达分析，我们之前观察到人血嗜酸性粒细胞表达IL-7Rα (CD127)及其共同γ链（γ - c, CD132）的mRNA。本研究的目的是确定嗜酸性粒细胞是否具有功能性IL-7受体，并通过评估IL-7在特应性哮喘患者支气管肺泡灌洗液（BAL）中的存在，评估IL-7对嗜酸性气道炎症的潜在贡献。免疫印迹分析显示CD127存在于高度纯化的人血嗜酸性粒细胞中。此外，嗜酸性粒细胞对IL-7的反应是STAT5的磷酸化，活化标记CD69的上调，以及生存时间的延长。中和GM-CSF，而不是IL-5，显著减弱了这些功能反应，表明IL-7通过促进自身GM-CSF的嗜酸性粒细胞释放来调节其作用。值得注意的是，抗gm - csf对STAT5磷酸化的抑制作用发生在嗜酸性粒细胞暴露于IL-7后10分钟内。因此，IL-7可能激活嗜酸性粒细胞释放预先形成的GM-CSF，而不是新合成的GM-CSF。在一项过敏性哮喘患者气道过敏原攻击的研究中，IL-7与体内嗜酸性粒细胞的生物学相关性受到了影响。部分过敏原攻击48 h后，BAL液中IL-7浓度显著升高，且与BAL嗜酸性粒细胞高度相关（r=0.7, p<0.001）。综上所述，气道对过敏原的反应与IL-7的产生有关，IL-7可能通过促进嗜酸性粒细胞的激活和生存而促进气道炎症。激活嗜酸性粒细胞是IL-7的一种新功能。
The primary function of IL-7 is to promote maturation and survival of T cells. Through microarray expression analysis, we previously observed that human blood eosinophils express mRNA for IL-7Rα (CD127) and its common gamma chain (γc, CD132). The purpose of this study was to determine if eosinophils have functional IL-7 receptors and to assess the potential contribution of IL-7 to eosinophilic airway inflammation by evaluating its presence in bronchoalveolar lavage (BAL) fluid of subjects with atopic asthma before and after segmental bronchoprovocation with allergen. Immunoblot analysis revealed that CD127 is present in highly purified human blood eosinophils. Furthermore, eosinophils responded to IL-7 with phosphorylation of STAT5, upregulation of the activation marker CD69, and prolonged survival. Neutralization of GM-CSF, but not IL-5, significantly blunted these functional responses, suggesting that IL-7 mediates its effects by promoting eosinophil release of autologous GM-CSF. Notably, the suppressive effect of anti-GM-CSF on STAT5 phosphorylation occurred within 10 min of eosinophil exposure to IL-7. Thus, IL-7 likely activates eosinophil release of preformed, rather than newly synthesized GM-CSF. The biological relevance of IL-7 to eosinophilia in vivo was implicated in a study of airway allergen challenge in allergic asthmatics. IL-7 concentrations in BAL fluid increased significantly 48 h after segmental allergen challenge and were highly correlated with BAL eosinophils (r=0.7, p<0.001). In conclusion, the airway response to allergen is associated with the generation of IL-7, which may contribute to airway inflammation by promoting enhanced eosinophil activation and survival. Activation of eosinophils is a novel function for IL-7.