High Mobility Group Box Protein 1: An Endogenous Signal for Dendritic Cell Maturation and Th1 Polarization
Abstract
High mobility group box protein 1 (HMGB1), a DNA binding nuclear and cytosolic protein, is a proinflammatory cytokine released by monocytes and macrophages. This study addressed the hypothesis that HMGB1 is an immunostimulatory signal that induces dendritic cell (DC) maturation. We show that HMGB1, via its B box domain, induced phenotypic maturation of DCs, as evidenced by increased CD83, CD54, CD80, CD40, CD58, and MHC class II expression and decreased CD206 expression. The B box caused increased secretion of the proinflammatory cytokines IL-12, IL-6, IL-1α, IL-8, TNF-α, and RANTES. B box up-regulated CD83 expression as well as IL-6 secretion via a p38 MAPK-dependent pathway. In the MLR, B box-activated DCs acted as potent stimulators of allogeneic T cells, and the magnitude of the response was equivalent to DCs activated by exposure to LPS, nonmethylated CpG oligonucleotides, or CD40L. Furthermore, B box induced secretion of IL-12 from DCs as well as IL-2 and IFN-γ secretion from allogeneic T cells, suggesting a Th1 bias. HMGB1 released by necrotic cells may be a signal of tissue or cellular injury that, when sensed by DCs, induces and/or enhances an immune reaction.
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When activated by DAMP-PRR binding, monocytes and macrophages produce proinflammatory cytokines, such as TNFα, IL-6, and IL-1.
“When activated by DAMP–PRR binding, monocytes and macrophages produce proinflammatory cytokines, such as TNFα, IL-6, and IL-1.72”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [72]
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- Authors
- Messmer, D., Yang, H., Telusma, G., Knoll, F., Li, J., Messmer, B., Tracey, K. J., & Chiorazzi, N.
- Affiliations
- North Shore University Hospital (US)
- Albert Einstein College of Medicine (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07-01
- Volume
- 173
- Issue
- 1
- Pages
- 307-313
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1896731228
- Cited by
- 447
- References
- 1
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 11 · 2022: 13 · 2021: 14 · 2020: 17 · 2019: 14 · 2018: 19 · 2017: 21 · 2016: 23 · 2015: 24 · 2014: 27 · 2013: 32 · 2012: 22
- FWCI
- 8.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- HMGB1, dendritic cell maturation, Th1 polarization, B-box domain, inflammatory cytokines, IL-12, interleukin-6, p38 MAPK, allogeneic T cell activation, CD83, necrosis, innate immune signaling, MHC class II expression
- MeSH terms
- CD83 Antigen, Amino Acid Sequence, Dendritic Cells, Humans, Immunoglobulins, Membrane Glycoproteins, Molecular Sequence Data, Antigens, CD, Interleukin-6, Cytokines, NF-kappa B, Cell Polarity, Th1 Cells, Chemokines, Mitogen-Activated Protein Kinases, HMGB1 Protein, p38 Mitogen-Activated Protein Kinases
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