Roles of G-protein coupled receptors in inflammation and immunity.

基于白三烯B4受体1(BLT1)在Th2淋巴细胞中高表达的发现，我们利用卵蛋白诱导的哮喘模型分析了BLT1的作用。BLT1基因缺失小鼠未出现气道高反应性、嗜酸性炎症和杯状细胞增生。症状减轻的同时伴随着IgE产生的减少，以及支气管肺泡灌洗液中IL-5和IL-13的积累，这表明BLT1基因缺失的小鼠的Th2型免疫反应减弱。致敏BLT1基因缺失小鼠的支气管周围淋巴结细胞在体外经抗原再次刺激后，其增殖和Th2细胞因子的产生明显减弱。因此，树突状细胞(DC)是控制Th1型和Th2型…的重要抗原提呈细胞。树突状细胞(DC)是重要的抗原提呈细胞通过释放细胞因子和直接与T细胞相互作用，产生更多的免疫反应。我们发现BLT1在人单核细胞来源的DC和小鼠骨髓来源的DC(BMDCs)中都有表达。使用BMDCs的详细分析表明，BLT1缺陷的DC产生的IL-L2p70比WT DC少，导致同种异体混合淋巴细胞反应中干扰素-α的产生减弱。BLT1缺陷树突状细胞过继转移到未成熟的WT小鼠体内后，小鼠的免疫功能减弱。与WT DC相比，体内Th1应答和Th2应答增强。BLT1基因缺陷小鼠的迟发性超敏反应(DTH)明显减弱，其中Th1型细胞反应起关键作用，诱导后BLT1基因缺陷小鼠的延髓淋巴结细胞与WT小鼠相比，Th1细胞因子的产生减少。因此，除了在炎症中的作用外，LTB4-BLT1轴在启动DC介导的Th1型免疫反应中也是重要的。我们将被报道为溶血磷脂受体的G2a受体鉴定为质子敏感型GPCR。较少

Based on the finding that leukotriene B_4 receptor 1 (BLT1) is expressed highly in Th2 lymphocytes, we analyzed the roles of BLT1 using an ovalbumin-induced bronchial asthma model. BLT1-null mice did not develop airway hyperresponsiveness, eosinophilic inflammation and hyperplasia of goblet cells. Attenuated symptoms were accompanied by reduced IgE production, and accumulation of IL-5 and IL-13 in bronchoalveolar lavage fluid, suggesting attenuated Th2-type immune response in BLT1-null mice. Peribronchial lymph node cells of sensitized BLT1-null mice showed much attenuated proliferation and production of Th2 cytokines upon re-stimulation with antigen in vitro. Thus, LTB_4-BLT1 axis is required for the development of Th2-type immune response, and blockade of LTB_4 functions through BLT1 would be novel and useful in the effort to ameliorate bronchial asthma and related Th2-biased immune disorders.Dendritic cells (DCs) are important antigen-presenting cells that control Th1- and Th2-type … More immunological reactions by releasing cytokines and interacting directly with T cells. We found that BLT1 is expressed in human monocyte-derived DCs and mouse bone marrow-derived DCs (BMDCs). Detailed analyses using BMDCs revealed that BLT1-deficient DCs produced less IL-l2 p70 than WT DCs, leading to attenuated IFN-□ production in an allogeneic mixed lymphocyte reaction. Adoptive transfer of BLT1-deficient DCs into naive WT mice induced a weakened. Th1 response and an 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.We characterized G2A receptor, which was reported as a lysophospholipid receptor, as a proton-sensing GPCR. Less