Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity
Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity
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DOI：
10.1038/nm1352
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发表时间：
2006-02-01
期刊：
影响因子：
82.9
通讯作者：
Housseau, F
中科院分区：
文献类型：
--
作者：
Chan, CW;Crafton, E;Housseau, F
自然杀伤（NK）细胞和树突状细胞（DC）分别是先天性和适应性免疫应答的中心组分（1，2）。我们在这里描述了第三个DC谱系，称为干扰素产生的杀伤DC（IKDC），不同于传统的DC和浆细胞样DC和NK细胞和DC的分子表达谱。它们产生大量的I型干扰素（IFN）和白细胞介素（IL）-12或IFN-c，这取决于激活刺激。在用Toll样受体（TLR）-9的配体CpG寡脱氧核苷酸刺激后，IKDC使用NK活化受体杀死典型的NK靶细胞。其细胞溶解能力随后降低，与NKG 2D受体（也称为Klrk 1）及其衔接子Dap 10和Dap 12的丢失相关。随着细胞毒性的丧失，获得了DC样抗原呈递活性，与表面主要组织相容性复合物II类（MHC II）和共刺激分子的上调相关，这正式将它们与经典NK细胞区分开来。在体内，脾脏IKDC优先显示NK功能，并且在全身感染时，迁移到淋巴结，在那里它们主要显示抗原呈递细胞活性。凭借其杀伤靶细胞的能力，随后进行抗原呈递，IKDC提供了先天性免疫和适应性免疫之间的联系。
Natural killer (NK) cells and dendritic cells (DCs) are, respectively, central components of innate and adaptive immune responses(1,2). We describe here a third DC lineage, termed interferon-producing killer DCs (IKDCs), distinct from conventional DCs and plasmacytoid DCs and with the molecular expression profile of both NK cells and DCs. They produce substantial amounts of type I interferons (IFN) and interleukin (IL)-12 or IFN-c, depending on activation stimuli. Upon stimulation with CpG oligodeoxynucleotides, ligands for Toll-like receptor (TLR)-9, IKDCs kill typical NK target cells using NK-activating receptors. Their cytolytic capacity subsequently diminishes, associated with the loss of NKG2D receptor (also known as Klrk1) and its adaptors, Dap10 and Dap12. As cytotoxicity is lost, DC-like antigen-presenting activity is gained, associated with upregulation of surface major histocompatibility complex class II (MHC II) and costimulatory molecules, which formally distinguish them from classical NK cells. In vivo, splenic IKDCs preferentially show NK function and, upon systemic infection, migrate to lymph nodes, where they primarily show antigen-presenting cell activity. By virtue of their capacity to kill target cells, followed by antigen presentation, IKDCs provide a link between innate and adaptive immunity.