Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo.
Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo.
复制标题
DOI：
10.1084/jem.20061297
复制
发表时间：
2006-10-02
影响因子：
15.3
通讯作者：
Koyasu, Shigeo
中科院分区：
文献类型：
--
作者：
Ohteki, Toshiaki;Tada, Hiroyuki;Ishida, Kazuto;Sato, Taku;Maki, Chikako;Yamada, Taketo;Hamuro, Junji;Koyasu, Shigeo
白细胞介素(IL)-15在多种炎症性疾病中表达。然而，树突状细胞（DC）衍生的IL-15对疾病发展的贡献尚不确定。利用已建立的痤疮丙酸杆菌（P. acnes）和酵素诱导的肝脏炎症模型，我们观察到野生型（WT）和RAG-2 - / -小鼠的肝脏形成肉芽肿，而IL-15 - / -小鼠的肝脏没有形成肉芽肿。我们证明，这可能是由于单核细胞迁移所需的IL-12、IFN-γ和趋化因子的顺序诱导受损引起的。同样，在P. acnes和zymosan2引物的IL-15 - / -小鼠或用新的IL-15中和抗体处理的WT小鼠中，没有诱导致死性内毒素休克。在这两个系统中，促炎细胞因子的产生都受到了损害。令人惊讶的是，在缺乏dc的小鼠中，既没有诱导肉芽肿形成、致死性内毒素休克，也没有诱导IL-15的产生，并且过继性转移WT而不是IL-15 - / - dc恢复了IL-15 - / -小鼠的疾病发展。总的来说，这些数据表明dc来源的IL-15作为体内炎症反应介质的重要性。
Interleukin (IL)-15 is expressed in a variety of inflammatory diseases. However, the contribution of dendritic cell (DC)–derived IL-15 to the development of diseases is uncertain. Using established models of Propionibacterium acnes (P. acnes)– and zymosan-induced liver inflammation, we observed granuloma formation in the livers of wild-type (WT) and RAG-2−/− mice but not in those of IL-15−/− mice. We demonstrate that this is likely caused by an impaired sequential induction of IL-12, IFN-γ, and chemokines necessary for monocyte migration. Likewise, lethal endotoxin shock was not induced in P. acnes– and zymosan-primed IL-15−/− mice or in WT mice treated with a new IL-15–neutralizing antibody. In both systems, proinflammatory cytokine production was impaired. Surprisingly, neither granuloma formation, lethal endotoxin shock, nor IL-15 production was induced in mice deficient for DCs, and adoptive transfer of WT but not IL-15−/− DCs restored the disease development in IL-15−/− mice. Collectively, these data indicate the importance of DC-derived IL-15 as a mediator of inflammatory responses in vivo.