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PMID: 15272298 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

HMGB1 is an endogenous immune adjuvant released by necrotic cells.

EMBO reports ·Vol. 5 ·No. 8 ·2004-08-00 ·Pages 825-30

Rovere-Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, Dumitriu IE, Müller S, Iannacone M, Traversari C, Bianchi ME, Manfredi AA

Abstract

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.

MeSH Terms
Adjuvants, Immunologic Animals Antigens, CD/immunology Cell Line Dendritic Cells/immunology Fibroblasts/cytology,physiology HMGB1 Protein/genetics,immunology,isolation & purification Humans Mice Mice, Inbred C57BL Mice, Knockout Necrosis
Chemicals
Adjuvants, Immunologic Antigens, CD HMGB1 Protein
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Rovere-Querini Patrizia
Cancer Immunotherapy & Gene Therapy Program, Clinical Immunology Unit H San Raffaele Scientific Institute and Vita-Salute San Raffaele University, DIBIT 3A1, Chromatin Dynamics Unit, Via Olgettina 58, 20132 Milano, Italy.
Capobianco Annalisa
Scaffidi Paola
Valentinis Barbara
Catalanotti Federica
Giazzon Marta
Dumitriu Ingrid E
Müller Susanne
Iannacone Matteo
Traversari Catia
Bianchi Marco E
Manfredi Angelo A
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1038/sj.embor.7400205
Published
2004-08-00
Epub
2004-00-23
Pages
825-30
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1299116
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.embor.7400205 PMC Full Text View journal details
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