Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
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DOI：
10.1084/jem.190.8.1155
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发表时间：
1999-10-18
期刊：
影响因子：
--
通讯作者：
Griffith TS
中科院分区：
文献类型：
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作者：
Fanger NA;Maliszewski CR;Schooley K;Griffith TS
肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis inducing ligand，TRAIL）是肿瘤坏死因子家族的一员，可诱导多种癌细胞凋亡。在这项研究中，我们证明了人CD 11 c+血液树突状细胞（DC）在干扰素（IFN）-γ或-α刺激后表达TRAIL，并获得杀死TRAIL敏感肿瘤细胞靶点的能力，但不杀死TRAIL耐药肿瘤细胞或正常细胞类型。DC介导的凋亡是TRAIL特异性的，因为可溶性TRAIL受体阻断靶细胞死亡。此外，IFN刺激的白细胞介素（IL）-3受体（R）α+血液前体（前）DC对相同的靶细胞显示出最小的细胞毒性，表明CD 11 c + DC和IL-3Rα+前DC亚群之间存在明显的功能差异。这些结果表明，TRAIL可能作为一种先天性效应分子对CD 11 c + DC自发产生的肿瘤细胞的消除，并提出了一种手段，其中TRAIL表达的DC可能会调节或消除T细胞响应的抗原提出的DC。
TRAIL (TNF-related apoptosis-inducing ligand) is a member of the TNF family that induces apoptosis in a variety of cancer cells. In this study, we demonstrate that human CD11c+ blood dendritic cells (DCs) express TRAIL after stimulation with either interferon (IFN)-γ or -α and acquire the ability to kill TRAIL-sensitive tumor cell targets but not TRAIL-resistant tumor cells or normal cell types. The DC-mediated apoptosis was TRAIL specific, as soluble TRAIL receptor blocked target cell death. Moreover, IFN-stimulated interleukin (IL)-3 receptor (R)α+ blood precursor (pre-)DCs displayed minimal cytotoxicity toward the same target cells, demonstrating a clear functional difference between the CD11c+ DC and IL-3Rα+ pre-DC subsets. These results indicate that TRAIL may serve as an innate effector molecule on CD11c+ DCs for the elimination of spontaneously arising tumor cells and suggest a means by which TRAIL-expressing DCs may regulate or eliminate T cells responding to antigen presented by the DCs.