Cited by 600Advanced Glycation End Products researchImmune Response and InflammationBiomarkers in Disease Mechanisms

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High‐mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity

Bianchi, Marco E., Manfredi, Angelo A.·2007·Immunological Reviews

DOI 10.1111/j.1600-065x.2007.00574.x

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Abstract

Summary: Tissue damage occurs often in the life of mammals and is usually repaired. Dying cells are swiftly phagocytosed, but before disappearing, they alert surrounding cells to activate homeostatic programs. They release signals that recruit inflammatory cells to the site of injury, promote cell migration and cell division to replace dead cells, and activate the immune system in anticipation of microbial invasion. Many of these events involve high‐mobility group box 1 protein (HMGB1), a nuclear protein that is released passively when necrotic cells lose the integrity of their membranes. HMGB1 behaves as a trigger of inflammation, attracting inflammatory cells, and of tissue repair, recruiting stem cells and promoting their proliferation. Moreover, HMGB1 activates dendritic cells (DCs) and promotes their functional maturation and their response to lymph node chemokines. Activated leukocytes actively secrete HMGB1 in the microenvironment. Thus, HMGB1 acts in an autocrine/paracrine fashion and sustains long‐term repair and defense programs. DCs secrete HMGB1 several hours after contact with the first maturation stimulus; HMGB1 secretion is critical for their ability to reach the lymph nodes, to sustain the proliferation of antigen‐specific T cells, to prevent their activation‐dependent apoptosis, and to promote their polarization towards a T‐helper 1 phenotype. These immune responses will also be directed against self‐antigens that DCs process at the time of injury and can lead to autoimmunity.

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Authors: Bianchi, M. E., & Manfredi, A. A.
Affiliations: Vita-Salute San Raffaele University (IT)
Corresponding author: Bianchi, Marco E.
ORCID: Bianchi, Marco E.
Manfredi, Angelo A.
Venue: Immunological Reviews
Publisher: Wiley
Published: 2007-10-30
Volume: 220
Issue: 1
Pages: 35-46
ISSN: 0105-2896 (ISSN-L)
1600-065X
DOI: 10.1111/j.1600-065x.2007.00574.x
OpenAlex: W2109590683
Cited by: 600
References: 86
Citations by year: 2026: 13 · 2025: 10 · 2024: 13 · 2023: 20 · 2022: 28 · 2021: 21 · 2020: 17 · 2019: 25 · 2018: 41 · 2017: 34 · 2016: 26 · 2015: 37 · 2014: 44 · 2013: 55 · 2012: 45
FWCI: 5.25
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Immunological Reviews (publishedVersion)
PubMed (publishedVersion)
Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
Funders: Associazione Italiana per la Ricerca sul Cancro
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Keywords: HMGB1, high mobility group box 1, innate immunity, adaptive immunity, inflammation, tissue repair, dendritic cell maturation, T cell activation, autoimmunity, necrosis, chemokines, stem cell recruitment, autocrine and paracrine signaling
MeSH terms: Animals, Dendritic Cells, Humans, Immunity, Innate, Lupus Erythematosus, Systemic, T-Lymphocytes, Autoimmunity, Sepsis, HMGB1 Protein, Toll-Like Receptors

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High‐mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity

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