Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
J Allergy Clin Immunol. 2012 Feb;129(2):483-91. doi: 10.1016/j.jaci.2011.07.051. Epub 2011 Sep 8.
The inhalation of diesel exhaust particles (DEPs) is associated with increased sensitization toward inhaled allergens. Dendritic cells (DCs) are important mediators in immune regulation. We previously showed that the inhalation of DEPs increased the accumulation of DCs in the lung and enhanced the T(H)2 response in the mediastinal lymph node.
We hypothesized that CC chemokine receptors CCR2, CCR5, and CCR6 critically mediate the DC recruitment upon exposure to DEPs and that these CC chemokine receptors are important in the DEP-induced T(H)2 response.
We exposed CCR2 knockout, CCR5 knockout, CCR6 knockout, and wild-type mice to DEPs and examined the pulmonary monocyte and DC accumulation. By an adoptive transfer experiment, we assessed the direct involvement of CCR2 and CCR6 in the recruitment of blood monocytes toward the lung upon exposure to DEPs. We also examined the T(H)2 cytokine production in the mediastinal lymph nodes of DEP-exposed CCR2 knockout and CCR6 knockout mice.
We observed that the DEP-induced monocyte and monocyte-derived DC recruitment was completely abolished in CCR2 knockout mice. CCR6 knockout mice also showed impaired monocyte recruitment upon exposure to DEPs. In contrast, monocyte and DC recruitment was comparable between DEP-exposed wild-type and CCR5 knockout mice. The impaired monocyte-derived DC recruitment in DEP-exposed CCR2 knockout, not CCR6 knockout, mice resulted in an abolished T(H)2 response in the mediastinal lymph node.
These data suggest that monocyte-derived DCs, recruited in a CCR2-dependent manner, are critical in inducing T(H)2 responses upon inhalation of DEPs.
吸入柴油机排气颗粒（DEPs）与对吸入性过敏原的致敏作用增加有关。树突状细胞（DCs）是免疫调节的重要介质。我们之前的研究表明，吸入 DEPs 会增加肺部 DC 的积累，并增强纵隔淋巴结中的 T(H)2 反应。
我们假设 CC 趋化因子受体 CCR2、CCR5 和 CCR6 在暴露于 DEPs 时对 DC 的募集具有重要的介导作用，并且这些 CC 趋化因子受体在 DEP 诱导的 T(H)2 反应中是重要的。
我们使 CCR2 敲除、CCR5 敲除、CCR6 敲除和野生型小鼠暴露于 DEPs，并检查肺部单核细胞和 DC 的积累。通过过继转移实验，我们评估了 CCR2 和 CCR6 在暴露于 DEPs 时直接参与血液单核细胞向肺部的募集。我们还检查了 DEP 暴露的 CCR2 敲除和 CCR6 敲除小鼠纵隔淋巴结中的 T(H)2 细胞因子产生。
我们观察到，DEPs 诱导的单核细胞和单核细胞衍生的 DC 募集在 CCR2 敲除小鼠中完全被消除。CCR6 敲除小鼠在暴露于 DEPs 时也显示出单核细胞募集受损。相比之下，DEP 暴露的野生型和 CCR5 敲除小鼠之间的单核细胞和 DC 募集无差异。DEP 暴露的 CCR2 敲除而非 CCR6 敲除小鼠中单核细胞衍生的 DC 募集受损导致纵隔淋巴结中的 T(H)2 反应被消除。
这些数据表明，以 CCR2 依赖的方式募集的单核细胞衍生的 DC 在吸入 DEPs 时诱导 T(H)2 反应是至关重要的。
