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High‐mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity, and tissue repair
Author(s) -
Bianchi Marco E.,
Crippa Massimo P.,
Manfredi Angelo A.,
Mezzapelle Rosanna,
Rovere Querini Patrizia,
Venereau Emilie
Publication year - 2017
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12601
Subject(s) - hmgb1 , inflammation , biology , immune system , innate immune system , damp , acquired immune system , microbiology and biotechnology , secretion , immunology , regeneration (biology) , wound healing , immunity , immunogenicity , biochemistry , physics , meteorology
Summary A single protein, HMGB 1, directs the triggering of inflammation, innate and adaptive immune responses, and tissue healing after damage. HMGB 1 is the best characterized damage‐associated molecular pattern ( DAMP ), proteins that are normally inside the cell but are released after cell death, and allow the immune system to distinguish between antigens that are dangerous or not. Notably, cells undergoing severe stress actively secrete HMGB 1 via a dedicated secretion pathway: HMGB 1 is relocated from the nucleus to the cytoplasm and then to secretory lysosomes or directly to the extracellular space. Extracellular HMGB 1 (either released or secreted) triggers inflammation and adaptive immunological responses by switching among multiple oxidation states, which direct the mutually exclusive choices of different binding partners and receptors. Immune cells are first recruited to the damaged tissue and then activated; thereafter, HMGB 1 supports tissue repair and healing, by coordinating the switch of macrophages to a tissue‐healing phenotype, activation and proliferation of stem cells, and neoangiogenesis. Inevitably, HMGB 1 also orchestrates the support of stressed but illegitimate tissues: tumors. Concomitantly, HMGB 1 enhances the immunogenicity of mutated proteins in the tumor (neoantigens), promoting anti‐tumor responses and immunological memory. Tweaking the activities of HMGB 1 in inflammation, immune responses and tissue repair could bring large rewards in the therapy of multiple medical conditions, including cancer.