High-mobility group box family of proteins: ligand and sensor for innate immunity

Recent discoveries in signal-transducing innate receptors have illustrated the close link between innate and adaptive immunity. These advances revisit a fundamental issue of immunology, the recognition of self and nonself molecules by the immune system. Indeed, mounting evidence has been provided that the sensing of self-derived molecules by the immune system is important for health and disease. The high-mobility group box (HMGB) proteins, particularly HMGB1, are self-derived immune activators that have multiple functions in the regulation of immunity and inflammation. In this review, we summarize current knowledge of the function of HMGB proteins, as a ligand that can evoke inflammatory responses, and as a sensor for nucleic-acid-mediated immune responses.