The role of HMGB1 in inflammatory skin diseases

High-mobility group box 1 protein (HMGB1) is a highly abundant, non-histone nuclear protein that can serve as an alarmin to promote the pathogenesis of inflammatory diseases. In response to various stimuli, HMGB1 can translocate from the nucleus to the cytoplasm as well as the extracellular space through passive or active release, accompanied with different post-translational modifications. Depending on the redox state of three cysteine residues, HMGB1 determines its activity to induce cytokine production or tissue repair through binding with several different receptors. In addition, HMGB1 can form immunostimulatory complexes with cytokines and other endogenous/exogenous molecules and synergistically enhance their biological effect. Cell death is an important source of HMGB1 and major cell death forms such as apoptosis, necrosis and pyroptosis can modulate the redox state of HMGB1. In various human skin diseases as well as animal models, HMGB1 levels in cytoplasm, tissue and blood are increased and blockade of HMGB1 at-tenuates disease severity in animal models. These findings indicate that HMGB1 can serve as a unique biomarker as well as a target of new therapy in many inflammatory skin diseases. (C) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Automated summary

HMGB1 is a highly abundant non-histone nuclear protein that can promote the pathogenesis of inflammatory diseases. It can translocate to the cytoplasm and extracellular space through release and modifications and induce cytokine production or tissue repair through receptor binding. It can also form complexes with cytokines and enhance their biological effects. Cell death is a significant source of HMGB1, and different forms of cell death can modulate its activity. Blocking HMGB1 can attenuate disease severity in skin diseases. Therefore, HMGB1 may serve as a biomarker and therapeutic target in inflammatory skin diseases.