Chan Ray Chun-Fai, Wang Meiying, Li Ning, Yanagawa Yoshiki, Onoé Kazunori, Lee James J, Nel Andre E
Division of Clinical Immunology and Allergy, Department of Medicine, University of California-Los Angeles, CA 90095, USA.
J Allergy Clin Immunol. 2006 Aug;118(2):455-65. doi: 10.1016/j.jaci.2006.06.006.
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).
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.
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.
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.
These data provide the first report that pro-oxidative 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.
These data clarify the adjuvant effect of particulate air pollutants in allergic inflammatory disease.
流行病学研究表明，暴露于环境颗粒物会导致哮喘加重。柴油尾气颗粒（DEP）作为一种典型污染物，可作为变应性致敏的佐剂。越来越多的证据表明，这种效应可能是通过对树突状细胞（DC）的作用介导的。
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变应原的免疫反应。
我们将小鼠骨髓来源的DC和一种同质髓样DC系BC1暴露于DEP及其有机提取物中，以确定氧化应激的诱导如何影响细胞成熟、细胞因子产生以及抗原特异性T细胞的激活。
DEP提取物在DC中诱导氧化应激。这种氧化还原平衡的变化干扰了Toll样受体激动剂诱导成熟受体（如CD86、CD54和I-A(d)）表达和IL-12产生的能力。DC功能的这种扰动伴随着抗原特异性T细胞中IFN-γ诱导减少和IL-10诱导增加。DC功能扰动的分子基础是激活抑制IL-12产生的核因子红细胞2（NF-E2）相关因子2介导的信号通路。NF-E2相关因子2缺陷消除了DEP对DC功能的扰动。
这些数据首次报道了促氧化DEP化学物质可在同质DC群体中干扰促进T(H)1的反应途径，并为DEP对变应性炎症的佐剂效应提供了新的解释。
这些数据阐明了空气中颗粒污染物在变应性炎症疾病中的佐剂效应。
