Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Japan.
J Intern Med. 2011 Oct;270(4):301-8. doi: 10.1111/j.1365-2796.2011.02433.x.
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.
中心保护和病理免疫是激活先天免疫反应识别核酸通过跨膜 Toll 样受体 (TLR) 和胞质受体。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，而视黄酸诱导基因-I (RIG-I)-样受体 (RLRs)、RIG-I 和 MDA5 被认为是胞质 RNA 感应受体。此外，包括 DAI、RIG-I/MDA5 和 AIM2 在内的胞质 DNA 感应受体也会引发先天免疫反应。高迁移率族蛋白 (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反应的激活。免疫反应的核酸介导激活存在一个层次结构，其中核酸感应受体的选择性激活取决于 HMGB 对核酸的更广泛感应。本文的目的是总结 HMGB 蛋白的这一新特征，作为核酸介导的先天免疫反应激活的重要前沿启动子。此外，我们将讨论这些发现的治疗意义。
