Terminal complement complex C5b-9-treated human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization
Terminal complement complex C5b-9-treated human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization
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末端补体复合物 C5b-9 处理的人单核细胞来源的树突状细胞经历成熟并诱导 Th1 极化
DOI：
10.1002/eji.200636285
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Wu, Yuzhang
中科院分区：
文献类型：
--
作者：
Chen, Yongwen;Yang, Chengying;Wu, Yuzhang
亚溶性C5b-9被描述为一种促炎介质，它触发细胞活化而不是诱导细胞死亡。树突状细胞（DC）在控制抗原特异性免疫反应中起着关键作用。虽然各种刺激诱导的DC成熟已经被很好地描述，但C5b-9在DC功能中的作用尚未被描述。在本报告中，我们使用基于纯化的远端补体蛋白体外组装的功能性C5b-9来证明亚水解C5b-9促进DC成熟。这可以通过CD83、hla抗原和共刺激分子CD80、D86、B7-1-11、B7-1-13、B7-1-14和BTLA的上调来证明。此外，在c5b -9处理的DC中，白细胞介素(IL)-12和肿瘤坏死因子-a等细胞因子的分泌增加，而抗原摄取能力（fitc -葡聚糖和路西弗黄）降低。混合淋巴细胞反应表明，csb -9激活的DC作为刺激剂，显著促进CD4(+) T细胞活化，并引发包括干扰素- γ和IL-2在内的细胞因子的产生。有趣的是，c5b -9处理的DC也将CD4(+)CD45RA（+）幼稚T细胞定向到Thl极化。我们的研究结果首次报道DC是C5b-9的潜在免疫调节靶点，表明C5b-9通过诱导DC成熟架起先天免疫和获得性免疫的桥梁。
Sublytic C5b-9 has been described as a pro-inflammatory mediator that triggers cell activation rather than inducing cell death. Dendritic cells (DC) play a critical role in controlling antigen-specific immune responses. Although DC maturation induced by various stimuli has been well characterized, the role of C5b-9 in DC function has not been described. In this report, we use in vitro assembled functional C5b-9 based on purified distal complement protein to show that DC maturation is promoted by sublytic C5b-9. This was demonstrated by up-regulation of CD83, HLA-antigens and costimulatory molecules, including CD80, D86, B7-1-11, B7-1-13, B7-1-14 and BTLA. In addition, secretion of cytokines such as interleukin (IL)-12 and tumor necrosis factor-a was increased while the capacity for antigen uptake (FITC-Dextran and Lucifer Yellow) was reduced in C5b-9-treated DC. Mixed lymphocyte reactions indicated that CSb-9-activated DC acted as stimulators that significantly promoted CD4(+) T cell activation and elicited production of cytokines, including interferon-gamma and IL-2. Interestingly, C5b-9-treated DC also orient CD4(+)CD45RA(+) naive T cells toward Thl polarization. Our results are the first to report that DC are potential immunoregulatory targets of C5b-9, suggesting that C5b-9 bridges innate and acquired immunity by inducing DC maturation.