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

Franklin, BS; Bossaller, L; De Nardo, D; Ratter, JM; Stutz, A; Engels, G; Brenker, C; Nordhoff, M; Mirandola, SR; Al-Amoudi, A; Mangan, MS; Zimmer, S; Monks, BG; Fricke, M; Schmidt, RE; Espevik, T; Jones, B; Jarnicki, AG; Hansbro, PM; Busto, P; Marshak-Rothstein, A; Hornemann, S; Aguzzi, A; Kastenmüller, W; Latz, E

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

Franklin, BS Bossaller, L De Nardo, D Ratter, JM Stutz, A Engels, G Brenker, C Nordhoff, M Mirandola, SR Al-Amoudi, A Mangan, MS Zimmer, S Monks, BG Fricke, M Schmidt, RE Espevik, T Jones, B Jarnicki, AG Hansbro, PM

Busto, P Marshak-Rothstein, A Hornemann, S Aguzzi, A Kastenmüller, W Latz, E

Permalink

Publication Type:: Journal Article
Citation:: Nature Immunology, 2014, 15 (8), pp. 727 - 737
Issue Date:: 2014-01-01

Closed Access

	Filename	Description	Size
	The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation.pdf	Published Version	2.04 MB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Franklin, BS	en_US
dc.contributor.author	Bossaller, L	en_US
dc.contributor.author	De Nardo, D	en_US
dc.contributor.author	Ratter, JM	en_US
dc.contributor.author	Stutz, A	en_US
dc.contributor.author	Engels, G	en_US
dc.contributor.author	Brenker, C	en_US
dc.contributor.author	Nordhoff, M	en_US
dc.contributor.author	Mirandola, SR	en_US
dc.contributor.author	Al-Amoudi, A	en_US
dc.contributor.author	Mangan, MS	en_US
dc.contributor.author	Zimmer, S	en_US
dc.contributor.author	Monks, BG	en_US
dc.contributor.author	Fricke, M	en_US
dc.contributor.author	Schmidt, RE	en_US
dc.contributor.author	Espevik, T	en_US
dc.contributor.author	Jones, B	en_US
dc.contributor.author	Jarnicki, AG	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Busto, P	en_US
dc.contributor.author	Marshak-Rothstein, A	en_US
dc.contributor.author	Hornemann, S	en_US
dc.contributor.author	Aguzzi, A	en_US
dc.contributor.author	Kastenmüller, W	en_US
dc.contributor.author	Latz, E	en_US
dc.date.available	2014-05-01	en_US
dc.date.issued	2014-01-01	en_US
dc.identifier.citation	Nature Immunology, 2014, 15 (8), pp. 727 - 737	en_US
dc.identifier.issn	1529-2908	en_US
dc.identifier.uri	http://hdl.handle.net/10453/138457
dc.description.abstract	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 1β (IL-1β) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular space, where they promoted further maturation of IL-1β. In addition, phagocytosis of ASC specks by macrophages induced lysosomal damage and nucleation of soluble ASC, as well as activation of IL-1β 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. © 2014 Nature America, Inc. All rights reserved.	en_US
dc.relation.ispartof	Nature Immunology	en_US
dc.relation.isbasedon	10.1038/ni.2913	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Lysosomes	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Pseudomonas aeruginosa	en_US
dc.subject.mesh	Pseudomonas Infections	en_US
dc.subject.mesh	Autoimmune Diseases	en_US
dc.subject.mesh	Inflammation	en_US
dc.subject.mesh	Caspase 1	en_US
dc.subject.mesh	Amino Acid Chloromethyl Ketones	en_US
dc.subject.mesh	Carrier Proteins	en_US
dc.subject.mesh	Cytoskeletal Proteins	en_US
dc.subject.mesh	Prions	en_US
dc.subject.mesh	Antibodies	en_US
dc.subject.mesh	Autoantibodies	en_US
dc.subject.mesh	Cell Communication	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Apoptosis	en_US
dc.subject.mesh	Phagocytosis	en_US
dc.subject.mesh	Apoptosis Regulatory Proteins	en_US
dc.subject.mesh	Interleukin-1beta	en_US
dc.subject.mesh	Inflammasomes	en_US
dc.subject.mesh	Caspase Inhibitors	en_US
dc.subject.mesh	NLR Family, Pyrin Domain-Containing 3 Protein	en_US
dc.subject.mesh	CARD Signaling Adaptor Proteins	en_US
dc.title	The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	15	en_US
utslib.for	1107 Immunology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	15	en_US

Abstract:

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 1β (IL-1β) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular space, where they promoted further maturation of IL-1β. In addition, phagocytosis of ASC specks by macrophages induced lysosomal damage and nucleation of soluble ASC, as well as activation of IL-1β 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. © 2014 Nature America, Inc. All rights reserved.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/138457