HMGB1 is an endogenous immune adjuvant released by necrotic cells

被引:499
作者
Rovere-Querini, P
Capobianco, A
Scaffidi, P
Valentinis, B
Catalanotti, F
Giazzon, M
Dumitriu, IE
Müller, S
Iannacone, M
Traversari, C
Bianchhi, ME
Manfredi, AA
机构
[1] H San Raffaele Sci Inst, Clin Immunol Unit, Canc Immunotherapy & Gene Therapy Program, I-20132 Milan, Italy
[2] Vita Salute San Raffele Univ, Chromatin Dynam Unit, I-20132 Milan, Italy
[3] Molmed SpA, I-20132 Milan, Italy
关键词
HMGB1; apoptosis; necrosis; innate immunity; immune adjuvants;
D O I
10.1038/sj.embor.7400205
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:825 / 830
页数:6
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