Complement C1q chemoattracts human dendritic cells and enhances migration of mature dendritic cells to CCL19 via activation of AKT and MAPK pathways
Complement C1q chemoattracts human dendritic cells and enhances migration of mature dendritic cells to CCL19 via activation of AKT and MAPK pathways
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补体 C1q 化学吸引人树突状细胞，并通过激活 AKT 和 MAPK 途径增强成熟树突状细胞向 CCL19 的迁移
DOI：
10.1016/j.molimm.2008.08.279
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发表时间：
2008-12-01
影响因子：
3.6
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
--
作者：
Liu, Shuxun;Wu, Jiang;Cao, Xuetao
树突状细胞（DC）和补体都是先天免疫的重要效应器，也是先天免疫和适应性免疫之间的有效链接者。作为先天免疫的关键成分，炎症部位产生的各种生物活性补体成分被发现能够调节 DC 的功能。众所周知，DC迁移到外周炎症部位有利于DC作为抗原呈递细胞识别和摄取入侵的病原体，DC迁移到次级淋巴组织有利于T细胞的打印和激活。然而，迄今为止，人们对经典途径第一个成员多功能分子C1q调节DC迁移的潜在信号机制知之甚少。在这项研究中，我们发现 C1q 介导未成熟 MoDC 的趋化性和跨内皮迁移。此外，C1q 通过上调 CCR7 表达，显着增强 LPS 诱导的成熟 DC 对 CCL19 的趋化性。未成熟DC对C1q的趋化性需要PI3K/AKT、ERK和JNK途径的激活，同时C1q介导的成熟DC对CCL19趋化性的增强需要AKT和P38途径的激活。因此，我们的结果表明，在炎症部位活跃产生和积累的C1q可以直接将未成熟的DC从血液趋化至外周炎症组织，并通过激活AKT和MAPK途径促进成熟的DC迁移至次级淋巴器官。从而概述了有利于先天免疫与适应性免疫联系的新方法。 (c) 2008 Elsevier Ltd. 保留所有权利。
Dendritic cells (DC) and complement are both important effectors in innate immunity, and also potent linkers between innate immunity and adaptive immunity. As key components of innate immunity, various bioactive complement components produced at the inflammatory sites have been found to be able to regulate functions of DC. It is well known that migration of DC to the peripheral inflammatory sites benefits the recognition and uptake of invading pathogens by DC as antigen-presenting cells, and DC migration to secondary lymphatic tissues benefits the printing and activation of T cells. However, up to date, little is known about the underlying signaling mechanisms for the regulation of DC migration by the multifunctional molecule C1q, the first member of classical pathway. In this study, we show that C1q mediates the chemotaxis and transendothelial migration of immature MoDC. Additionally, C1q significantly enhances the chemotaxis of LPS-induced mature DC to CCL19 via upregulation of CCR7 expression. Activation of PI3K/AKT, ERK and JNK pathways is required for the chemotaxis of immature DC to C1q, meanwhile activation of AKT and P38 pathways is required for the C1q-mediated enhancement of mature DC chemotaxis to CCL19. Therefore, our results Suggest that C1q, actively produced and accumulated at the inflammatory sites, can directly chemoattract immature DC from blood to peripheral inflammatory tissues, and promotes the migration of mature DC to secondary lymph organs via activation of AKT and MAPK pathways. thus Outlining new way for favoring the link of innate immunity to adaptive immunity. (c) 2008 Elsevier Ltd. All rights reserved.