In vivo IL-10 gene delivery suppresses airway eosinophilia and hyperreactivity by down-regulating APC functions and migration without impairing the antigen-specific systemic immune response in a mouse model of allergic airway inflammation
In vivo IL-10 gene delivery suppresses airway eosinophilia and hyperreactivity by down-regulating APC functions and migration without impairing the antigen-specific systemic immune response in a mouse model of allergic airway inflammation
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DOI：
10.4049/jimmunol.174.11.6955
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发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Yamamoto, K
中科院分区：
文献类型：
--
作者：
Nakagome, K;Dohi, M;Yamamoto, K
IL-10是一种抗肿瘤细胞因子。尽管先前的研究报道外源性递送IL-10可减轻实验性过敏性气道炎症中的气道炎症，但其作用机制尚未完全阐明。在这份报告中，我们阐明了IL-10在体内的作用机制。免疫BALM小鼠，用OVA-Ag气溶胶攻击。我们在全身致敏前或通过施用产生IL-10的质粒载体在气溶胶Ag激发期间将IL-10基因递送给小鼠。不仅如所报道的IL-10的预致敏递送，而且在炎症期间的递送强烈抑制气道嗜酸性粒细胞增多和高反应性的发展。预致敏递送抑制了肺和脾中的Ag特异性Th 2型免疫应答。与此相反，在效应阶段的交付抑制Th 2的反应，只有在肺，而在脾不受影响。IL-10基因的传递并不诱导T细胞或树突状细胞的调节表型的发展;相反，它抑制了肺的CD 11 c（+）APC的整体功能，如Ag呈递能力、细胞因子产生和OVA-Ag向淋巴结的转运，从而减轻了Th 2介导的过敏性气道炎症。此外，IL-10在Ag和APC的存在下显示出明显的免疫抑制作用。这些结果表明，抑制APC功能在肺，免疫反应的网站，发挥了关键作用，在IL-10介导的抑制银诱导的气道炎症和高反应性。因此，如果选择性地递送，IL-10可以位点特异性地抑制Ag特异性免疫应答而不影响全身免疫应答。
IL-10 is an inummostappressive cytokine. Although previous studies have reported that exogenous delivery of IL-10 reduced airway inflammation in experimental allergic airway inflammation, the mechanism of action has not been fully clarified. In this report, we elucidated a mechanism of action of IL-10 in vivo. BALM mice were immunized and aerosol challenged with OVA-Ag. We delivered the IL-10 gene to the mice before systemic sensitization or during aerosol Ag challenge by administering an IL-10-producing plasmid vector. Not only presensitization delivery of IL-10, as reported, but also delivery during inflammation strongly suppressed the development of airway eosinophilia and hyperreactivity. Presensitization delivery suppressed the Ag-specific Th2-type immune response in both the lung and spleen. In contrast, delivery in the effector phase suppressed the Th2 response only in the lung, whereas that in the spleen was not affected. IL-10 gene delivery did not induce the development of a regulatory phenotype of T cells or dendritic cells; rather, it suppressed the overall functions of CD11c(+) APCs of the lung such as Ag-presenting capacity, cytokine production, and transportation of OVA-Ag to lymph nodes, thus attenuating Th2-mediated allergic airway inflammation. Further, IL-10 revealed a distinct immunosuppressive effect in the presence of Ag and APCs. These results suggest that suppression of APC function in the lung, the site of immune response, played a critical role in the IL-10-mediated suppression of Ag-induced airway inflammation and hyperreactivity. Therefore, if delivered selectively, IL-10 could site specifically suppress the Ag-specific immune response without affecting systemic immune responses.