IFN-α inhibits IL-3 priming of human basophil cytokine secretion but not leukotriene C4 and histamine release
IFN-α inhibits IL-3 priming of human basophil cytokine secretion but not leukotriene C4 and histamine release
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DOI：
10.1016/j.jaci.2003.08.027
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发表时间：
2003-11-01
影响因子：
14.2
通讯作者：
Schroeder, JT
中科院分区：
文献类型：
--
作者：
Chen, YH;Bieneman, AP;Schroeder, JT
背景资料：先天免疫应答在决定获得性免疫过程中起关键作用，包括与过敏性疾病相关的免疫。在这些反应的早期产生的I型干扰素是引发T（H）1样活性的重要可溶性因子。目的：由于人嗜碱性粒细胞在响应IgE依赖性和IgE非依赖性刺激时分泌IL-4和IL-13，我们测试了IFN-α（一种主要的I型IFN）是否影响这些T（H）2细胞因子的产生和/或这些细胞的介质释放。在存在和不存在IL-3引发的情况下，用IFN-α处理从血液中分离的嗜碱性粒细胞，然后通过IgE受体刺激以释放组胺、白三烯C-4和IL-4。还测试了IFN-α对IL-3介导的IL-13分泌和嗜碱性粒细胞存活的影响。结果：IFN-a特异性抑制IL-3对嗜碱性细胞分泌细胞因子的影响。在与IFN-α同时培养的细胞中，由IL-3引发引起的IL-4分泌增强被显著抑制。这种效应是特定的细胞因子的产生，因为组胺和白三烯C4不受影响。此外，IFN-α阻断由IL-3直接诱导的IL-13分泌。虽然IFN-β也具有一定的抑制活性，但IFN-γ（一种II型IFN）对嗜碱性粒细胞的细胞因子分泌没有影响。嗜碱性粒细胞组成型表达的mRNA的I型IFN受体，IFN-α并没有影响嗜碱性粒细胞的生存能力方面的抑制细胞因子secretory.Conclusions：这些结果支持的信念，早期先天免疫反应，导致IFN-α的生产负调节过敏反应，也抑制启动嗜碱性粒细胞的细胞因子释放。
Background: Innate immune responses play a critical role in determining the course of acquired immunity, including that associated with allergic disease. Type I interferons, which are generated early in these reactions, are important soluble factors that prime for T(H)1-like activity.Objective: Because human basophils secrete IL-4 and IL-13 in response to both IgE-dependent and IgE-independent stimuli, we tested whether IFN-alpha, a major type I IFN, affects the production of these T(H)2 cytokines and/or mediator release from these cells.Methods: Basophils isolated from blood were treated with IFN-alpha in the presence and absence of IL-3 priming before stimulating through the IgE receptor to release histamine, leukotriene C-4, and IL-4. Effects of IFN-alpha on IL-3-mediated IL-13 secretion and basophil survival were also tested. IFN-a receptor expression was determined by RT-PCR.Results: IFN-alpha specifically inhibited the effects IL-3 has on basophil cytokine secretion. Enhanced secretion of IL-4 resulting from IL-3 priming was significantly inhibited in cells concurrently cultured with IFN-alpha. This effect was specific for cytokine generation, because histamine and leukotriene C4 were unaffected. Furthermore, IFN-alpha blocked IL-13 secretion directly induced by IL-3. Although IFN-beta also possessed some inhibitory activity, IFN-gamma (a type II IFN) had no effect on basophil cytokine secretion. Basophils constitutively expressed mRNA for the type I IFN receptor, and IFN-alpha did not affect basophil viability with regard to inhibition of cytokine secretion.Conclusions: These results support the belief that early innate immune responses resulting in IFN-alpha production negatively regulate allergic responses by also inhibiting priming of basophil cytokine release.