Essential role of high-mobility group box proteins in nucleic acid-mediated innate immune responses
Article first published online: 19 SEP 2011
© 2011 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 270, Issue 4, pages 301–308, October 2011
How to Cite
Yanai, H., Ban, T. and Taniguchi, T. (2011), Essential role of high-mobility group box proteins in nucleic acid-mediated innate immune responses. Journal of Internal Medicine, 270: 301–308. doi: 10.1111/j.1365-2796.2011.02433.x
- Issue published online: 19 SEP 2011
- Article first published online: 19 SEP 2011
- Accepted manuscript online: 27 JUL 2011 11:46AM EST
- high-mobility group box proteins;
- innate immunity;
- nucleic acids;
- pattern recognition receptors
Abstract. Yanai H, Ban T, Taniguchi T (The University of Tokyo; and Japan Science and Technology Agency; Tokyo, Japan). Essential role of high-mobility group box proteins in nucleic acid-mediated innate immune responses (Symposium). J Intern Med 2011; 270: 301–308.
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.