High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal

Nat Rev Immunol. 2005 Apr;5(4):331-42. doi: 10.1038/nri1594.


High-mobility group box 1 protein (HMGB1), which previously was thought to function only as a nuclear factor that enhances transcription, was recently discovered to be a crucial cytokine that mediates the response to infection, injury and inflammation. These observations have led to the emergence of a new field in immunology that is focused on understanding the mechanisms of HMGB1 release, its biological activities and its pathological effects in sepsis, arthritis, cancer and other diseases. Here, we discuss these features of HMGB1 and summarize recent advances that have led to the preclinical development of therapeutics that modulate HMGB1 release and activity.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm
  • Cell Nucleus / immunology
  • HMGB1 Protein / immunology*
  • Humans
  • Immune System / immunology*
  • Membrane Glycoproteins / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • Receptors, Cell Surface / metabolism
  • Signal Transduction / immunology*
  • Signal Transduction / physiology
  • Toll-Like Receptors


  • Antigens, Neoplasm
  • HMGB1 Protein
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • MOK protein, human
  • Mitogen-Activated Protein Kinases