A cell-surface molecule selectively expressed on murine natural interferon-producing cells that blocks secretion of interferon-alpha
A cell-surface molecule selectively expressed on murine natural interferon-producing cells that blocks secretion of interferon-alpha
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DOI：
10.1182/blood-2003-09-3108
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发表时间：
2004-06-01
期刊：
影响因子：
20.3
通讯作者：
Colonna, M
中科院分区：
文献类型：
--
作者：
Blasius, A;Vermi, W;Colonna, M
天然干扰素产生细胞(IPC)通过Toll样受体(TLR)9识别某些病毒和含有脱氧胞苷-磷酸-脱氧鸟苷(CpG)基序的DNA，从而分泌干扰素-α、白介素12(IL-12)和促炎趋化因子。人类IPC主要存在于发炎的淋巴结中，推测它们是从血液中招募的，以激活对微生物感染的先天和适应性反应。在小鼠感染模型中证明IPC的募集和功能一直是困难的，因为需要多种抗体才能将IPC与其他免疫细胞区分开来，而且从淋巴结中可以回收的IPC非常少。在这里，我们描述了一种在正常和炎症条件下都能检测到所有淋巴器官中的小鼠IPC的单抗。利用这种抗体，我们证明了IPC通常存在于淋巴结和脾的T细胞区，并且用炎性刺激接种外周组织可以触发IPC重新聚集到前哨淋巴结，无论这些刺激是否能够通过TLR直接刺激IPC。值得注意的是，我们发现IPC在体外与抗体孵育或在体内注射抗体显著减少CpG DNA反应中干扰素-α的分泌，而不会导致IPC耗尽。因此，抗体识别IPC特异性表面分子，当参与时，抑制干扰素-α的分泌。(C)2004年，由美国血液病学会提供。
Natural interferon (IFN)-producing cells (IPCs) recognize certain viruses and DNA containing deoxycytidylate-phosphate-deoxyguanylate (CpG) motifs through the toll-like receptor (TLR) 9, resulting in secretion of IFN-alpha, interleukin 12 (IL-12), and proinflammatory chemokines. Human IPCs are found mainly in inflamed lymph nodes, where they are presumably recruited from the blood to activate both innate and adaptive responses to microbial infections. Demonstrating IPC recruitment and function in murine infection models has been difficult because multiple antibodies are required to distinguish IPCs from other immune cells and very few IPCs can be recovered from lymph nodes. Here we describe a monoclonal antibody (mAb) that exclusively detects murine IPCs in all lymphoid organs under both normal and inflammatory conditions. Using this antibody, we demonstrate that IPCs are normally present in the T-cell zone of lymph nodes and spleen and that inoculation of peripheral tissues with inflammatory stimuli triggers recruitment of IPC into sentinel lymph nodes, whether the stimuli are able to directly stimulate IPCs through TLR or not. Remarkably, we show that incubation of IPCs with the antibody in vitro or administration of the antibody in vivo dramatically reduce secretion of IFN-alpha in response to CpG DNA without causing IPC depletion. Thus, the antibody identifies an IPC-specific surface molecule that, when engaged, inhibits IFN-alpha secretion. (C) 2004 by The American Society of Hematology.