Cutting Edge: A TLR9 Cytoplasmic Tyrosine Motif Is Selectively Required for Proinflammatory Cytokine Production
Cutting Edge: A TLR9 Cytoplasmic Tyrosine Motif Is Selectively Required for Proinflammatory Cytokine Production
复制标题
DOI：
10.4049/jimmunol.1102713
复制
发表时间：
2012-01-15
影响因子：
4.4
通讯作者：
Leifer, Cynthia Anne
中科院分区：
文献类型：
--
作者：
Chockalingam, Annapoorani;Rose, William Alfred, II;Leifer, Cynthia Anne
感测TLR 9的核酸的区室化已经被认为是防止识别自身核酸结构的机制。此外，在不同的内体区室中识别CpG DNA导致促炎细胞因子TNF-α或I型IFN的产生。我们以前的特点是酪氨酸基序在氨基酸888-891的TLR 9的细胞质尾重要的适当的细胞内定位。在这篇文章中，我们表明，这个主题是选择性地需要生产的TNF，但不是IFN。响应于CpG DNA刺激，蛋白水解处理的80-kDa片段被酪氨酸磷酸化。虽然Y888本身不是磷酸化的，但该基序的结构对于响应CpG DNA的TLR 9磷酸化和TNF-α产生都是必需的。我们的结论是，TLR 9信号的分叉是由一个关键的酪氨酸基序在胞质尾调控。免疫学杂志，2012，188：527-530。
Compartmentalization of nucleic acid sensing TLR9 has been implicated as a mechanism to prevent recognition of self nucleic acid structures. Furthermore, recognition of CpG DNA in different endosomal compartments leads to the production of the proinflammatory cytokine TNF-alpha, or type I IFN. We previously characterized a tyrosine-based motif at aa 888-891 in the cytoplasmic tail of TLR9 important for appropriate intracellular localization. In this article, we show that this motif is selectively required for the production of TNF, but not IFN. In response to CpG DNA stimulation, the proteolytically processed 80-kDa fragment is tyrosine phosphorylated. Although Y888 is not itself phosphorylated, the structure of this motif is necessary for both TLR9 phosphorylation and TNF-alpha production in response to CpG DNA. We conclude that bifurcation in TLR9 signaling is regulated by a critical tyrosine motif in the cytoplasmic tail. The Journal of Immunology, 2012, 188: 527-530.