The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation

被引：611

作者：

Franklin, Bernardo S. ^{[1
]}

Bossaller, Lukas ^{[2
,3
]}

De Nardo, Dominic ^{[1
]}

Ratter, Jacqueline M. ^{[1
]}

Stutz, Andrea ^{[1
]}

Engels, Gudrun ^{[1
]}

Brenker, Christoph ^{[4
]}

Nordhoff, Mark ^{[4
]}

Mirandola, Sandra R. ^{[4
]}

Al-Amoudi, Ashraf ^{[4
]}

Mangan, Matthew S. ^{[1
,4
]}

Zimmer, Sebastian ^{[5
]}

Monks, Brian G. ^{[1
,3
]}

Fricke, Martin ^{[2
]}

Schmidt, Reinhold E. ^{[2
]}

Espevik, Terje ^{[6
]}

Jones, Bernadette ^{[7
]}

Jarnicki, Andrew G. ^{[7
]}

Hansbro, Philip M. ^{[7
]}

Busto, Patricia ^{[3
]}

Marshak-Rothstein, Ann ^{[3
]}

Hornemann, Simone ^{[8
]}

Aguzzi, Adriano ^{[8
]}

Kastenmueller, Wolfgang ^{[9
]}

Latz, Eicke ^{[1
,3
,4
,6
]}

机构：

[1] Univ Bonn, Univ Hosp, Inst Innate Immun, Bonn, Germany

[2] Hannover Med Sch, Dept Immunol & Rheumatol, Hannover, Germany

[3] Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA USA

[4] German Ctr Neurodegenerat Dis, Bonn, Germany

[5] Univ Bonn, Univ Hosp, Dept Med Cardiol, Bonn, Germany

[6] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Ctr Mol Inflammat Res, N-7034 Trondheim, Norway

[7] Univ Newcastle, Ctr Asthma & Resp Dis, Newcastle, NSW 2300, Australia

[8] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland

[9] Univ Bonn, Univ Hosp, Inst Mol Med & Expt Immunol, Bonn, Germany

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 08期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

INNATE IMMUNE-RESPONSE; TOLL-LIKE RECEPTORS; NALP3; INFLAMMASOME; STERILE INFLAMMATION; CASPASE-1; ACTIVATION; SIGNAL-TRANSDUCTION; NLRP3; CELL-DEATH; PROTEIN; POLYMERIZATION;

D O I：

10.1038/ni.2913

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks recruit and activate caspase-1, which induces maturation of the cytokine interleukin 1 beta (IL-1 beta) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular space, where they promoted further maturation of IL-1 beta. In addition, phagocytosis of ASC specks by macrophages induced lysosomal damage and nucleation of soluble ASC, as well as activation of IL-1 beta in recipient cells. ASC specks appeared in bodily fluids from inflamed tissues, and autoantibodies to ASC specks developed in patients and mice with autoimmune pathologies. Together these findings reveal extracellular functions of ASC specks and a previously unknown form of cell-to-cell communication.

引用

页码：727 / +

页数：13

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