Yanai Hideyuki
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo.
Uirusu. 2011 Dec;61(2):141-52. doi: 10.2222/jsv.61.141.
The activation of innate immune responses by nucleic acids is critical to host responses against pathogens, such as viruses; however, nucleic acids can also trigger the development and/or exacerbation of pathogenic responses such as autoimmunity. We previously demonstrated that the selective activation of nucleic acid-sensing cytosolic and Toll-like receptors is contingent on the promiscuous sensing of nucleic acids by high-mobility group box proteins (HMGBs). Basides these findings, we also found that nonimmunogenic nucleotide with high-affinity HMGB binding, termed ISM ODN, functions as suppressing agent for nucleic acid-activated innate immune responses. In this review, we aim to summerize this novel feature of HMGB proteins in nucleic acid-mediated innate immune responses. In addition, we will discuss the inhibitory effect of nonimmunogenic oligodeoxynucleotides (ni-ODNs) targeting HMGB proteins.
核酸激活先天性免疫反应对于宿主对抗病原体（如病毒）的反应至关重要；然而，核酸也可引发致病性反应（如自身免疫）的发展和/或加剧。我们先前证明，核酸传感胞质受体和Toll样受体的选择性激活取决于高迁移率族蛋白（HMGBs）对核酸的混杂传感。除了这些发现，我们还发现与HMGB具有高亲和力结合的非免疫原性核苷酸（称为ISM ODN）可作为核酸激活的先天性免疫反应的抑制剂。在这篇综述中，我们旨在总结HMGB蛋白在核酸介导的先天性免疫反应中的这一新特性。此外，我们将讨论靶向HMGB蛋白的非免疫原性寡脱氧核苷酸（ni-ODNs）的抑制作用。
