HMGB1 is an endogenous immune adjuvant released by necrotic cells

Patrizia Rovere-Querini, Annalisa Capobianco, Paola Scaffidi, Barbara Valentinis, Federica Catalanotti, Marta Giazzon, Ingrid E Dumitriu, Susanne Müller, Matteo Iannacone, Catia Traversari, Marco E Bianchi, Angelo A Manfredi

Research output: Contribution to journalArticlepeer-review

484 Citations (Scopus)


Immune responses against pathogens require that microbial components promote the activation of antigen-presenting cells (APCs). Autoimmune diseases and graft rejections occur in the absence of pathogens; in these conditions, endogenous molecules, the so-called 'innate adjuvants', activate APCs. Necrotic cells contain and release innate adjuvants; necrotic cells also release high-mobility group B1 protein (HMGB1), an abundant and conserved constituent of vertebrate nuclei. Here, we show that necrotic HMGB1(-/-) cells have a reduced ability to activate APCs, and HMGB1 blockade reduces the activation induced by necrotic wild-type cell supernatants. In vivo, HMGB1 enhances the primary antibody responses to soluble antigens and transforms poorly immunogenic apoptotic lymphoma cells into efficient vaccines.

Original languageEnglish
Pages (from-to)825-30
Number of pages6
JournalEMBO Reports
Issue number8
Publication statusPublished - Aug 2004


  • Adjuvants, Immunologic
  • Animals
  • Antigens, CD/immunology
  • Cell Line
  • Dendritic Cells/immunology
  • Fibroblasts/cytology
  • HMGB1 Protein/genetics
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Necrosis


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