The Role of HMGB1 in Immunity

Decades of research have uncovered a variety of molecular mechanisms by which High-mobility group box-1 (HMGB1), also known as HMG1 or Amphoterin, in both immune and non-immune cells, modulate the type and magnitude of immune responses. This ubiquitous, highly conserved protein, HMGB1, was originally discovered in 1973 as a nuclear non-histone protein. The pro-inflammatory activity of extracellular HMGB1 was first discovered as a late mediator of endotoxin lethality in 1999. These findings were explored in the early 2000s in a series of reports elucidating cellular signals activated through HMGB1 receptors including RAGE, toll-like receptor 2 (TLR2), TLR4 and C-X-C chemokine receptor 4 (CXCR4). Post-translational modifications of HMGB1 including oxidation, influence its secretion and function. A substantial number of studies have demonstrated that HMGB1 has a central role in the pathogenesis of many systemic inflammatory diseases such as sepsis, cancer, ischemic injury, neuroinflammation mediated disorders and cognitive dysfunctions. There is robust clinical evidence for HMGB1 levels as a potential biomarker which can be used for early prediction and progression of various diseases. In recent days, HMGB1-targeted therapies have been exploited in multiple preclinical studies of inflammatory conditions. Nevertheless, there is a need to learn more about the important functional roles exerted by both intracellular and extracellular HMGB1 in immune and immune-related functions including: i) What might be the primary clinical indications for HMGB1 blockade? ii) What effects HMGB1 might have on the microenvironments of inflammation? iii) Are there unidentified novel immune receptors of HMGB1? iv) What is the secretion mechanism of leaderless HMGB1? v) What is the relevance of redox change of HMGB1 in diseases?

In this Research Topic, we welcome the submission of Reviews, Mini-Reviews, Brief Research Reports, Perspective, Original Research and Clinical Trial articles focusing on, but not limited to, the following topics:

1. HMGB1-related immune functions.
2. Post-translational modification and secretion mechanisms of HMGB1.
3. Specific molecular pathways activated by HMGB1 in possible human diseases of inflammation, sepsis, neurological diseases, and cancers.
4. New innovative reagents to modulate HMGB1 secretion or function.
5. Modulating HMGB1 for cancer treatment

These submissions will provide a comprehensive overview of the role and modulation of HMGB1 and HMGB1 specific therapeutics in various diseases.