Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Biochimie. 2010 Jun;92(6):682-91. doi: 10.1016/j.biochi.2009.12.002. Epub 2009 Dec 23.
Dendritic cells (DCs) are important antigen-presenting cells that control Th1- and Th2-type immunological reactions by releasing cytokines and interacting directly with T cells. Leukotriene B4 (LTB4), a classical proinflammatory lipid mediator for phagocytes, was recently identified as an important attractant for effector CD4(+) and CD8(+) T cells. However, little information is available on the roles of LTB4 and its receptor BLT1 in DCs. Here we show that functional BLT1 expressed in mouse bone marrow-derived DCs (BMDCs) plays important role in initiating Th1-type immune response. Detailed analyses using BMDCs revealed that BLT1-deficient DCs produced less IL-12p70 than WT DCs, leading to attenuated IFN-gamma production in an allogeneic mixed lymphocyte reaction. Adoptive transfer of antigen-loaded BLT1-deficient DCs into naïve WT mice induced a weakened Th1- and enhanced Th2-response in vivo compared to WT DCs. BLT1-deficient mice consistently showed much attenuated delayed-type hypersensitivity (DTH), in which Th1-type cellular responses play a key role, and popliteal lymph node cells of BLT1-deficient mice showed reduced production of Th1 cytokines after DTH induction compared to cells from WT mice. Thus, in addition to its role in inflammation, the LTB4-BLT1 axis is important in initiating Th1-type immunological reactions mediated by DCs.
树突状细胞 (DCs) 是重要的抗原呈递细胞，通过释放细胞因子并直接与 T 细胞相互作用来控制 Th1 和 Th2 型免疫反应。白三烯 B4（LTB4）是一种经典的吞噬细胞促炎脂质介质，最近被确定为效应 CD4(+)和 CD8(+)T 细胞的重要趋化因子。然而，关于 LTB4 和其受体 BLT1 在 DCs 中的作用的信息很少。在这里，我们表明在小鼠骨髓来源的树突状细胞（BMDCs）中表达的功能性 BLT1 在启动 Th1 型免疫反应中发挥重要作用。使用 BMDCs 的详细分析表明，BLT1 缺陷型 DCs 比 WT DCs 产生更少的 IL-12p70，导致同种异体混合淋巴细胞反应中 IFN-γ产生减少。将负载抗原的 BLT1 缺陷型 DCs 过继转移到 naive WT 小鼠体内，与 WT DCs 相比，在体内诱导较弱的 Th1 反应和增强的 Th2 反应。BLT1 缺陷型小鼠持续表现出明显减弱的迟发型超敏反应 (DTH)，其中 Th1 型细胞反应发挥关键作用，并且 BLT1 缺陷型小鼠的后肢淋巴结细胞在 DTH 诱导后产生的 Th1 细胞因子减少与 WT 小鼠的细胞相比。因此，除了在炎症中的作用外，LTB4-BLT1 轴在由 DCs 介导的 Th1 型免疫反应的起始中也很重要。
