Essential role of high-mobility group box proteins in nucleic acid-mediated innate immune responses
Essential role of high-mobility group box proteins in nucleic acid-mediated innate immune responses
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DOI：
10.1111/j.1365-2796.2011.02433.x
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发表时间：
2011-10-01
影响因子：
11.1
通讯作者：
Taniguchi, T.
中科院分区：
文献类型：
--
作者：
Yanai, H.;Ban, T.;Taniguchi, T.
保护性免疫和病理性免疫的核心是通过跨膜toll样受体（TLRs）和细胞质受体识别核酸时激活先天免疫反应。在哺乳动物中，跨膜模式识别受体TLR3、TLR7和TLR9分别识别双链RNA、单链RNA和低甲基化DNA，而维甲酸诱导基因i （RIG-I）样受体（RLRs）、RIG-I和MDA5是已知的细胞质内RNA感应受体。此外，包括DAI、RIG-I/MDA5和AIM2在内的胞质dna感应受体也能触发先天免疫反应。高迁移率组盒（HMGB） 1、2和3蛋白也与免疫原性核酸结合，通常参与核酸受体介导的先天免疫应答的激活。在核酸介导的免疫应答激活中有一个层次，其中核酸感应受体的选择性激活取决于hmgb对核酸的更混杂的感应。本文综述的目的是总结HMGB蛋白作为核酸介导的先天免疫应答激活的重要一线刺激物的新特征。此外，我们将讨论这些发现的治疗意义。
Central to protective and pathological immunity is the activation of innate immune responses upon recognition of nucleic acids by transmembrane Toll-like receptors (TLRs) and cytosolic receptors. In mammals, the transmembrane pattern recognition receptors TLR3, TLR7 and TLR9 recognize double-stranded RNA, single-stranded RNA and hypomethylated DNA, respectively, while the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), RIG-I and MDA5 are known to be cytosolic RNA-sensing receptors. In addition, cytosolic DNA-sensing receptors that include DAI, RIG-I/MDA5 and AIM2 also trigger innate immune responses. High-mobility group box (HMGB) 1, 2 and 3 proteins, which also bind immunogenic nucleic acids, are generally involved in the nucleic acid receptor-mediated activation of innate immune responses. There is a hierarchy in the nucleic acid-mediated activation of immune responses, wherein the selective activation of the nucleic acid-sensing receptors is contingent on the more promiscuous sensing of nucleic acids by HMGBs. The aim of this review is to summarize this novel feature of HMGB proteins, as essential frontline instigators of nucleic acid-mediated activation of innate immune responses. In addition, we will discuss the therapeutic implications of these findings.