IFN-α enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells
IFN-α enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells
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DOI：
10.1093/intimm/14.4.367
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发表时间：
2002-04-01
影响因子：
4.4
通讯作者：
Maraskovsky, E
中科院分区：
文献类型：
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作者：
Luft, T;Luetjens, P;Maraskovsky, E
I 型干扰素是在感染早期分泌的免疫调节细胞因子。 I 型 IFN 连接人类和小鼠的先天性免疫系统和适应性免疫系统。我们比较了 I 型和 II 型 IFN 诱导单核细胞来源的树突状细胞 (MoDC) 功能成熟的能力。扩展我们早期观察到的 I 型 IFN 促进 DC 成熟的观察，我们报告这些细胞因子还通过增强 MoDC 的 CD40 配体 (CD40L) 诱导的细胞因子分泌来增强 DC 分化。与其他刺激相比，单独的 I 型 IFN 是 MoDC 成熟的较差诱导剂。它们上调了HLA-DR、CD80、CD86、部分CCR7而非CD83的表达，部分降低了抗原摄取功能，增加了IL-12p35 mRNA的水平，并延长了肽-MHC I类复合物的表面表达以呈递至细胞毒性T淋巴细胞，但不诱导向CCL21趋化因子的迁移。然而，I 型干扰素是 CD40L 介导功能的有效辅助因子。在这里，他们增强了 CD40L 介导的 IL-6、IL-10 和 IL-12p70 分泌。此外，当与IL-1β和/或IL-4组合时，IFN-α2a I型IFN将CD40L介导的IL-12p70产量增加2至3倍，并使IL-12 p40/p70比率偏向于IFN-γ诱导的p70异二聚体，这与同种异体T细胞亚群和NK细胞更高水平的IFN-γ分泌相关。我们的结果表明，CD40L、IFN 和 IL-1beta 在感染和炎症部位的快速表达可以协同作用于未成熟的 DC，从而将先天性和适应性免疫反应联系起来。通过这种方式，I型IFN发挥双重作用：DC成熟因子和CD40L介导的DC活化增强剂。
Type I IFN are immune modulatory cytokines that are secreted during early stages of infection. Type I IFN bridge the innate and the adaptive immune system in humans and mice. We compared the capacity of type I and II IFN to induce the functional maturation of monocyte-derived dendritic cells (MoDC). Extending our earlier observation that type I IFN promote DC maturation, we report that these cytokines also enhance DC differentiation by augmenting CD40 ligand (CD40L)-induced cytokine secretion by MoDC. Type I IFN alone were poor inducers of MoDC maturation as compared with other stimuli. They up-regulated the expression of HLA-DR, CD80, CD86, partially CCR7 but not CD83, partially reduced antigen-uptake function, increased the levels of IL-12p35 mRNA, and prolonged surface expression of peptide-MHC class I complexes for presentation to cytotoxic T lymphocytes, but did not induce migration towards CCL21 chemokine. However, type I IFN were potent co-factors for CD40L-mediated function. Here, they enhanced CD40L-mediated IL-6, IL-10 and IL-12p70 secretion. Furthermore, when combined with IL-1beta and/or IL-4, IFN-alpha2a type I IFN increased CD40L-mediated IL-12p70 production by 2- to 3-fold, and biased the IL-12 p40/p70 ratio towards the IFN-gamma inducing p70 heterodimer, this correlating with higher levels of IFN-gamma secretion by allogeneic T cell subsets and NK cells. Our results suggest that the rapid expression of CD40L, IFN and IL-1beta at sites of infection and inflammation can act in concert on immature DC, thereby linking innate and adaptive immune responses. In this way, type I IFN play a dual role as DC maturation factors and enhancers of CD40L-mediated DC activation.