Abstract
Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the best-characterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases.
Original language | English |
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Pages (from-to) | 2184-90 |
Number of pages | 7 |
Journal | European Journal of Immunology |
Volume | 35 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jul 2005 |
Keywords
- Autocrine Communication/immunology
- Cell Differentiation/immunology
- Cells, Cultured
- Dendritic Cells/cytology
- HMGB1 Protein/biosynthesis
- Humans
- Interferon-alpha/metabolism
- Membrane Glycoproteins/metabolism
- Receptor for Advanced Glycation End Products
- Receptors, Cell Surface/metabolism
- Receptors, Immunologic/biosynthesis
- Toll-Like Receptor 9
- Toll-Like Receptors