Genome wide transcriptional analysis of resting and IL2 activated human natural killer cells: gene expression signatures indicative of novel molecular signaling pathways.
Genome wide transcriptional analysis of resting and IL2 activated human natural killer cells: gene expression signatures indicative of novel molecular signaling pathways.
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DOI：
10.1186/1471-2164-8-230
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发表时间：
2007-07-10
期刊：
影响因子：
4.4
通讯作者：
Chan WC
中科院分区：
文献类型：
--
作者：
Dybkaer K;Iqbal J;Zhou G;Geng H;Xiao L;Schmitz A;d'Amore F;Chan WC
人类自然杀伤(NK)细胞是天然免疫反应的关键贡献者，这些细胞的效应功能被白细胞介素2(IL2)等细胞因子所增强。我们利用全基因组转录图谱来确定从健康捐献者的外周血中分离的静息和IL2激活的NK细胞中的基因表达特征和途径。静息NK细胞的基因表达谱显示多种细胞毒因子、细胞因子、趋化因子以及抑制和激活表面NK受体的高表达。静息NK细胞表达许多与细胞静止相关的基因，并具有活跃的转化生长因子β(TGFB1)信号通路。IL2刺激诱导细胞静止相关基因迅速下调，与细胞周期进程和增殖相关的基因上调。激活受体(DNAM1、KLRC1和KLRC3)、死亡受体配体(TNFSF6(FASL和TRAIL))、趋化因子受体(CX3CR1、CCR5和CCR7)、白介素受体(IL2RG、IL18RAb和IL27RA)以及分泌途径成员(DEGS1、FKBP11、SSR3、SEC61G和SLC3A2)表达上调。表达谱提示PI3K/AKT激活和NF-κB激活是通过多条途径(TLRIL1R、TCR样可能涉及Bcl10)实现的。许多途径成员和下游靶基因的表达增加支持了NFAT信号的激活。转录因子GATA3在静息细胞中表达，而T-BET在激活时表达上调，同时细胞因子表达谱发生变化。NK细胞在先天性免疫反应中的重要性也反映在炎性趋化因子以及参与黏附和淋巴细胞运输或迁移的受体和分子的晚期表达增加。这一分析使我们能够识别与细胞静止有关的基因，以及准备立即做出免疫反应的细胞因子和细胞毒因子。这也使我们能够观察到IL2对NK细胞的序贯免疫刺激作用，提高了我们对NK细胞激活背后的生物学和分子介质的理解。
Human natural killer (NK) cells are the key contributors of innate immune response and the effector functions of these cells are enhanced by cytokines such as interleukine 2 (IL2). We utilized genome-wide transcriptional profiling to identify gene expression signatures and pathways in resting and IL2 activated NK cell isolated from peripheral blood of healthy donors. Gene expression profiling of resting NK cells showed high expression of a number of cytotoxic factors, cytokines, chemokines and inhibitory and activating surface NK receptors. Resting NK cells expressed many genes associated with cellular quiescence and also appeared to have an active TGFβ (TGFB1) signaling pathway. IL2 stimulation induced rapid downregulation of quiescence associated genes and upregulation of genes associated with cell cycle progression and proliferation. Numerous genes that may enhance immune function and responsiveness including activating receptors (DNAM1, KLRC1 and KLRC3), death receptor ligand (TNFSF6 (FASL) and TRAIL), chemokine receptors (CX3CR1, CCR5 and CCR7), interleukin receptors (IL2RG, IL18RAB and IL27RA) and members of secretory pathways (DEGS1, FKBP11, SSR3, SEC61G and SLC3A2) were upregulated. The expression profile suggested PI3K/AKT activation and NF-κB activation through multiple pathways (TLR/IL1R, TNF receptor induced and TCR-like possibly involving BCL10). Activation of NFAT signaling was supported by increased expression of many pathway members and downstream target genes. The transcription factor GATA3 was expressed in resting cells while T-BET was upregulated on activation concurrent with the change in cytokine expression profile. The importance of NK cells in innate immune response was also reflected by late increased expression of inflammatory chemotactic factors and receptors and molecules involved in adhesion and lymphocyte trafficking or migration. This analysis allowed us to identify genes implicated in cellular quiescence and the cytokines and cytotoxic factors ready for immediate immune response. It also allowed us to observe the sequential immunostimulatory effects of IL2 on NK cells improving our understanding of the biology and molecular mediators behind NK cell activation.
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DOI：
10.1186/1476-9433-1-2
发表时间：
2002-11-18
期刊：
Medical immunology (London, England)
影响因子：
--
作者：
Beadling, Carol;Smith, Kendall A
通讯作者：
Smith, Kendall A
影响因子：
4.4
作者：
Loos, A;Glanemann, C;Sinskey, AJ
通讯作者：
Sinskey, AJ
影响因子：
64.5
作者：
Macián, F;García-Cózar, F;Rao, A
通讯作者：
Rao, A
影响因子：
30.5
作者：
Avni, O;Lee, D;Rao, A
通讯作者：
Rao, A
在人类天然杀伤细胞中，活化T细胞NFATP和NFATC的核因子的激活和表达：CD16配体结合时调节。
DOI：
10.1084/jem.182.3.801
发表时间：
1995-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Aramburu J;Azzoni L;Rao A;Perussia B
通讯作者：
Perussia B