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

doi:10.1038/sj.embor.7400205

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

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

484 Citations (Scopus)

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.

Original language	English
Pages (from-to)	825-30
Number of pages	6
Journal	EMBO Reports
Volume	5
Issue number	8
DOIs	https://doi.org/10.1038/sj.embor.7400205
Publication status	Published - Aug 2004

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.embor.7400205

Cite this

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title = "HMGB1 is an endogenous immune adjuvant released by necrotic cells",

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.",

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author = "Patrizia Rovere-Querini and Annalisa Capobianco and Paola Scaffidi and Barbara Valentinis and Federica Catalanotti and Marta Giazzon and Dumitriu, {Ingrid E} and Susanne M{\"u}ller and Matteo Iannacone and Catia Traversari and Bianchi, {Marco E} and Manfredi, {Angelo A}",

year = "2004",

month = aug,

doi = "10.1038/sj.embor.7400205",

language = "English",

volume = "5",

pages = "825--30",

journal = "EMBO Reports",

issn = "1469-221X",

publisher = "EMBO Press",

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T1 - HMGB1 is an endogenous immune adjuvant released by necrotic cells

AU - Rovere-Querini, Patrizia

AU - Capobianco, Annalisa

AU - Scaffidi, Paola

AU - Valentinis, Barbara

AU - Catalanotti, Federica

AU - Giazzon, Marta

AU - Dumitriu, Ingrid E

AU - Müller, Susanne

AU - Iannacone, Matteo

AU - Traversari, Catia

AU - Bianchi, Marco E

AU - Manfredi, Angelo A

PY - 2004/8

Y1 - 2004/8

N2 - 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.

AB - 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.

KW - Adjuvants, Immunologic

KW - Animals

KW - Antigens, CD/immunology

KW - Cell Line

KW - Dendritic Cells/immunology

KW - Fibroblasts/cytology

KW - HMGB1 Protein/genetics

KW - Humans

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Necrosis

U2 - 10.1038/sj.embor.7400205

DO - 10.1038/sj.embor.7400205

M3 - Article

C2 - 15272298

SN - 1469-221X

VL - 5

SP - 825

EP - 830

JO - EMBO Reports

JF - EMBO Reports

IS - 8

ER -

HMGB1 is an endogenous immune adjuvant released by necrotic cells

Abstract

Keywords

UN SDGs

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