Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation
Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation
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DOI：
10.1016/j.jaci.2006.06.006
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发表时间：
2006-08-01
影响因子：
14.2
通讯作者：
Nel, Andre E.
中科院分区：
文献类型：
--
作者：
Chan, Ray Chun-Fai;Wang, Meiying;Nel, Andre E.
背景：流行病学研究表明，暴露于环境颗粒物可导致哮喘急性发作。柴油机排气颗粒物（DEPs）是一种典型的污染物，可作为过敏性致敏的佐剂。越来越多的证据表明，这种作用可能是通过对树突状细胞（DCs）的作用来介导的。目的：我们的目的是阐明促氧化DEP化学物质改变DC功能的机制，从而使这些抗原呈递细胞增强对实验性过敏原的免疫应答。我们暴露了小鼠骨髓来源的DC和一个同质的骨髓DC系，BC 1，对DEP和由这些颗粒制成的有机提取物进行分析，以确定氧化应激的诱导如何影响细胞成熟、细胞因子产生和抗原特异性T细胞的活化。DEP提取物诱导DCs氧化应激。氧化还原平衡的这种变化干扰了Toll样受体激动剂诱导成熟受体（例如，CD 86、CD 54和I-A（d））表达和IL-12产生的能力。这种DC功能的扰动伴随着抗原特异性T细胞中IFN-γ的减少和IL-10诱导的增加。DC功能扰动的分子基础是核因子-红细胞2（NF-E2）相关因子2介导的抑制IL-12产生的信号通路的激活。NF-E2-related factor 2 deficiencies aborted disturbance of DC function by DEPs.Conclusion：这些数据提供了第一个报告，prooxidative DEP化学品可以干扰T（H）1-promoting response pathways in a homogeneous DC population，并提供了一个新的解释DEPs对过敏性炎症的佐剂效应。
Background: Epidemiologic studies show that exposure to ambient particulate matter leads to asthma exacerbation. Diesel exhaust particles (DEPs), a model pollutant, act as an adjuvant for allergic sensitization. Increasing evidence shows that this effect could be mediated by an effect on dendritic cells (DCs).Objective: Our aim was to elucidate the mechanism by which pro-oxidative DEP chemicals change DC function so that these antigen-presenting cells strengthen the immune response to an experimental allergen.Methods: We exposed murine bone marrow-derived DCs and a homogeneous myeloid DC line, BC1, to DEPs and organic extracts made from these particles to determine how the induction of oxidative stress affects cellular maturation, cytokine production, and activation of antigen-specific T cells.Results: DEP extracts induced oxidative stress in DCs. This change in redox equilibrium interfered in the ability of Toll-like receptor agonists to induce the expression of maturation receptors (eg, CD86, CD54, and I-A(d)) and IL-12 production. This perturbation of DC function was accompanied by decreased IFN-gamma and increased IL-10 induction in antigen-specific T cells. The molecular basis for the perturbation of DC function is the activation of a nuclear factor-erythroid 2 (NF-E2)-related factor 2-mediated signaling pathway that suppresses IL-12 production. NF-E2-related factor 2 deficiency abrogates the perturbation of DC function by DEPs.Conclusion: These data provide the first report that prooxidative DEP chemicals can interfere in T(H)1-promoting response pathways in a homogeneous DC population and provide a novel explanation for the adjuvant effect of DEPs on allergic inflammation.