Cited by 692Advanced Glycation End Products researchImmune Response and InflammationSystemic Lupus Erythematosus Research

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HMGB1: A multifunctional alarmin driving autoimmune and inflammatory disease

Harris, Helena Erlandsson, Andersson, Ulf, Pisetsky, David S.·2012·Nature Reviews Rheumatology

DOI 10.1038/nrrheum.2011.222

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Abstract

HMGB1 is a non-histone nuclear protein that can serve as an alarmin to drive the pathogenesis of inflammatory and autoimmune disease. Although primarily located in the cell nucleus, HMGB1 can translocate to the cytoplasm, as well as the extracellular space, during cell activation and cell death; during activation, HMGB1 can undergo post-translational modifications. The activity of HMGB1 varies with the redox states of the cysteine residues, which are required for binding to TLR4. In addition to stimulating cells directly, HMGB1 can form immunostimulatory complexes with cytokines and other endogenous and exogenous factors. In the synovia of patients with rheumatoid arthritis, as well as animal models of this disease, extranuclear expression of HMGB1 is increased and blockade of HMGB1 expression attenuates disease in animal models. In systemic lupus erythematosus, HMGB1 can be a component of immune complexes containing anti-DNA because of its interaction with DNA. In myositis, expression of HMGB1 is enhanced in inflamed muscle and can perturb muscle function. Together, these findings indicate that HMGB1 might be an important mediator and biomarker in rheumatic diseases as well as a target of new therapy.

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Authors: Harris, H. E., Andersson, U., & Pisetsky, D. S.
Affiliations: Karolinska Institutet (SE)
Karolinska University Hospital (SE)
Durham VA Medical Center (US)
Corresponding author: Pisetsky, David S.
ORCID: Harris, Helena Erlandsson
Pisetsky, David S.
Venue: Nature Reviews Rheumatology
Publisher: Springer Science and Business Media LLC
Published: 2012-01-31
Volume: 8
Issue: 4
Pages: 195-202
ISSN: 1759-4790 (ISSN-L)
1759-4804
DOI: 10.1038/nrrheum.2011.222
OpenAlex: W1972204333
Cited by: 689
References: 93
Citations by year: 2026: 20 · 2025: 31 · 2024: 32 · 2023: 34 · 2022: 54 · 2021: 61 · 2020: 50 · 2019: 59 · 2018: 65 · 2017: 57 · 2016: 53 · 2015: 52 · 2014: 55 · 2013: 49 · 2012: 16
FWCI: 6.55
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Rheumatology (publishedVersion)
PubMed (publishedVersion)
Funders: Vetenskapsrådet
Reumatikerförbundet
National Institutes of Health
National Institute of Allergy and Infectious Diseases (AI-056363, U19AI056363)
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
Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Keywords: HMGB1, alarmins, non-histone nuclear proteins, rheumatoid arthritis, systemic lupus erythematosus, myositis, inflammation, autoimmune disease, TLR4, post-translational modification, cysteine redox state, extracellular HMGB1, immune complexes, anti-DNA antibodies, synovium, biomarkers, therapeutic target
MeSH terms: Animals, Autoimmune Diseases, DNA-Binding Proteins, Humans, Inflammation, Rheumatic Diseases, Signal Transduction, HMGB1 Protein

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HMGB1: A multifunctional alarmin driving autoimmune and inflammatory disease

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