Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL)
Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL)
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DOI：
10.1182/blood-2005-08-3419
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
Liu, YJ
中科院分区：
文献类型：
--
作者：
Hanabuchi, S;Watanabe, N;Liu, YJ
浆细胞样树突状细胞前体(PDC)是专职的I型干扰素产生细胞，是调节先天免疫反应和获得性免疫反应的关键细胞类型。基因芯片基因表达分析发现，病毒或CpG-ODN激活的DC优先表达糖皮质激素诱导的肿瘤坏死因子受体(GITRL)的配体，逆转录聚合酶链式反应(RT-PCR)和流式细胞仪分析证实了这一点。用同样的方法，我们发现GITR是由激活的自然杀伤(NK)细胞和T细胞表达的。我们发现，CpG-ODN激活的pDC通过I型IFN和GITRL促进NK细胞的细胞毒作用和干扰素-γ的产生。使用GITRL转基因细胞株，我们进一步证明GITRL通过与白细胞介素2(IL-2)、干扰素-α和NKG2D触发协同作用，促进NK细胞的细胞毒作用和干扰素-γ的产生。我们还发现PDCs定位于扁桃体的T细胞区域，与NK细胞密切接触，并且有一部分PDCs表达GITRL。本研究揭示了GITR/GITRL在PDC介导的NK细胞共激活中的新功能。
Plasmacytoid dendritic cell precursors (pDCs) are professional type I interferon-producing cells, a critical cell type in regulating innate and adaptive immune responses. By microarray gene expression analysis, we found that pDCs activated by virus or CpG-ODN preferentially express the ligand for the glucocorticoid-induced tumor necrosis factor receptor (GITRL), which was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry analysis. Using the same approaches, we found GITR is expressed by activated natural killer (NK) cells and T cells. We show that pDCs activated by CpG-ODN promote NK cell cytotoxicity and interferon (IFN)-gamma production through type I IFNs and GITRL. Using a GITRL-transfected cell line, we further demonstrate that GITRL promotes NK cell cytotoxicity and IFN-gamma production in synergy with interleukin-2 (IL-2), IFN-alpha, and NKG2D triggering. We also demonstrated that pDCs localized in close contact to NK cells in T-cell areas of the tonsils, and a subpopulation of the pDCs expressed GITRL. This study reveals a novel function of GITR/GITRL in pDC-mediated coactivation of NK cells.