Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells
Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells
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DOI：
10.1182/blood-2005-07-2709
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发表时间：
2006-03-15
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：
Ito, T;Kanzler, H;Liu, YJ
最近的研究表明，pleismacytoid predendritic cells （pDCs）和myeloid dendritic cells （mDCs）具有产生相似数量的1型干扰素（ifn）和白细胞介素-12 （IL-12）的功能可塑性，挑战了具有不同功能的DC亚群的概念和存在。在这项研究中，我们证明了先前的研究表明，由于污染了多氯联苯，人类多氯联苯产生了大量的IL-12。使用高度纯化的人DC亚群，我们发现尽管在所有toll样受体配体和CD40配体的反应中，pDCs产生的ifn - α是mDCs的300倍，mDCs产生的IL-12 p70是pDCs的13倍，但pDCs在激活后的前12小时内迅速产生大量ifn - α，并且对进一步的刺激变得难以抑制。pDCs优先表达对IFN型至关重要的转录因子，但不表达IL-12转录因子，并且它们将60%的新转录活性用于制造19种1型IFN亚型。这项研究提供了正式的证据，证明DC子集的可塑性是有限的，不同的DC子集在连接先天免疫和适应性免疫中发挥不同的功能。
Recent studies suggest pleismacytoid predendritic cells (pDCs) and myeloid dendritic cells (mDCs) have the functional plasticity to produce similar amounts of type 1 interferons (IFNs) and interleukin-12 (IL-12), challenging the concept and existence of DC subsets with distinct function. In this study, we demonstrate that previous studies showed human pDCs produce large amounts of IL-12 because of contaminating mDCs. Using highly purified human DC subsets, we found that although pDCs make 300 times more IFN-alpha than mDCs and mDCs make 13 times more IL-12 p70 than pDCs in response to all the toll-like receptor ligands and CD40 ligands, pDCs rapidly make large amounts of IFN-alpha within the first 12 hours of activation and become refractory to further stimulation. pDCs preferentially expressed the transcriptional factors critical for type IFN, but not for IL-12 transcription, and they dedicated 60% of new transcriptional activity to make 19 type 1 IFN subtypes. This study provides formal proof that the plasticity of DC subsets is limited and that different DC subsets evolve to perform distinct functions in linking innate and adaptive immunity.