Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

Ingrid Dumitriu, Paramita Baruah, Marco E Bianchi, Angelo A Manfredi, Patrizia Rovere-Querini

Research output: Contribution to journalArticlepeer-review

159 Citations (Scopus)


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 languageEnglish
Pages (from-to)2184-90
Number of pages7
JournalEuropean Journal of Immunology
Issue number7
Publication statusPublished - Jul 2005


  • 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


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