Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation.
Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation.
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DOI：
10.1084/jem.20091573
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发表时间：
2010-11-22
期刊：
影响因子：
--
通讯作者：
Seya T
中科院分区：
文献类型：
--
作者：
Ebihara T;Azuma M;Oshiumi H;Kasamatsu J;Iwabuchi K;Matsumoto K;Saito H;Taniguchi T;Matsumoto M;Seya T
新的polyI：C诱导的膜蛋白INAM触发树突状细胞介导的自然杀伤细胞活化。在髓样树突状细胞（mDC）中，TLR 3在内体膜中表达并与含有衔接子toll/白介素1受体同源结构域的衔接子分子1（TICAM-1; TRIF）相互作用。TICAM-1信号在干扰素（IFN）调节因子（IRF）3激活中达到顶峰。用TLR 3配体polyI：C预处理的mDC和自然杀伤（NK）细胞的共培养导致NK细胞活化。这种激活是由细胞与细胞接触而不是细胞因子触发的。使用mDC基因的表达谱和功能获得/丧失分析，我们试图鉴定参与mDC介导的NK活化的TICAM-1诱导膜蛋白。在筛选的9个候选者中，有一个含有四跨膜蛋白样序列并满足筛选标准。这种蛋白质被称为IRF-3依赖性NK激活分子（INAM），在mDC和NK细胞中起作用，以促进NK激活。在mDC中，TICAM-1、IFN启动子刺激因子1和IRF-3是mDC介导的NK激活所需的，而不是IRF-7。INAM在NK细胞上最低限度地表达，响应于polyI：C而上调，并通过其胞质尾区促进mDC-NK相互激活，这对NK细胞中的激活信号至关重要。将表达INAM的mDC连续转移到植入NK敏感性肿瘤的小鼠中引起NK介导的肿瘤消退。我们确定了mDC-NK接触介导的NK激活的新途径，该途径由TLR信号衍生的膜分子控制。
The novel polyI:C-inducible membrane protein INAM triggers dendritic cell–mediated natural killer cell activation. In myeloid dendritic cells (mDCs), TLR3 is expressed in the endosomal membrane and interacts with the adaptor toll/interleukin 1 receptor homology domain–containing adaptor molecule 1 (TICAM-1; TRIF). TICAM-1 signals culminate in interferon (IFN) regulatory factor (IRF) 3 activation. Co-culture of mDC pretreated with the TLR3 ligand polyI:C and natural killer (NK) cells resulted in NK cell activation. This activation was triggered by cell-to-cell contact but not cytokines. Using expression profiling and gain/loss-of-function analyses of mDC genes, we tried to identify a TICAM-1–inducing membrane protein that participates in mDC-mediated NK activation. Of the nine candidates screened, one contained a tetraspanin-like sequence and satisfied the screening criteria. The protein, referred to as IRF-3–dependent NK-activating molecule (INAM), functioned in both the mDC and NK cell to facilitate NK activation. In the mDC, TICAM-1, IFN promoter stimulator 1, and IRF-3, but not IRF-7, were required for mDC-mediated NK activation. INAM was minimally expressed on NK cells, was up-regulated in response to polyI:C, and contributed to mDC–NK reciprocal activation via its cytoplasmic tail, which was crucial for the activation signal in NK cells. Adoptive transfer of INAM-expressing mDCs into mice implanted with NK-sensitive tumors caused NK-mediated tumor regression. We identify a new pathway for mDC–NK contact-mediated NK activation that is governed by a TLR signal-derived membrane molecule.
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DOI：
10.1084/jem.20010938
发表时间：
2002-02-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gerosa F;Baldani-Guerra B;Nisii C;Marchesini V;Carra G;Trinchieri G
通讯作者：
Trinchieri G
影响因子：
32.4
作者：
Lucas, Mathias;Schachterle, William;Diefenbach, Andreas
通讯作者：
Diefenbach, Andreas
影响因子：
82.9
作者：
Fernandez, NC;Lozier, A;Zitvogel, L
通讯作者：
Zitvogel, L
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
DOI：
10.1073/pnas.201238598
发表时间：
2001-09-25
影响因子：
11.1
作者：
Cerwenka, A;Baron, JL;Lanier, LL
通讯作者：
Lanier, LL