2.50
Hdl Handle:
http://hdl.handle.net/10033/621270
Title:
The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury.
Authors:
Hu, Bo; Jin, Chengcheng; Li, Hua-Bing; Tong, Jiyu; Ouyang, Xinshou; Cetinbas, Naniye Malli; Zhu, Shu; Strowig, Till; Lam, Fred C; Zhao, Chen; Henao-Mejia, Jorge; Yilmaz, Omer; Fitzgerald, Katherine A; Eisenbarth, Stephanie C; Elinav, Eran; Flavell, Richard A
Abstract:
Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents. Mechanistically, we found that AIM2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. Our results suggest that AIM2 may be a new therapeutic target for ionizing radiation exposure.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. 2016, 354 (6313):765-768 Science
Journal:
Science (New York, N.Y.)
Issue Date:
2016
URI:
http://hdl.handle.net/10033/621270
DOI:
10.1126/science.aaf7532
PubMed ID:
27846608
Type:
Article
Language:
en
ISSN:
1095-9203
Appears in Collections:
publications of the research group microbial immune regulation (MIKI)

Full metadata record

DC FieldValue Language
dc.contributor.authorHu, Boen
dc.contributor.authorJin, Chengchengen
dc.contributor.authorLi, Hua-Bingen
dc.contributor.authorTong, Jiyuen
dc.contributor.authorOuyang, Xinshouen
dc.contributor.authorCetinbas, Naniye Mallien
dc.contributor.authorZhu, Shuen
dc.contributor.authorStrowig, Tillen
dc.contributor.authorLam, Fred Cen
dc.contributor.authorZhao, Chenen
dc.contributor.authorHenao-Mejia, Jorgeen
dc.contributor.authorYilmaz, Omeren
dc.contributor.authorFitzgerald, Katherine Aen
dc.contributor.authorEisenbarth, Stephanie Cen
dc.contributor.authorElinav, Eranen
dc.contributor.authorFlavell, Richard Aen
dc.date.accessioned2018-02-08T15:48:26Z-
dc.date.available2018-02-08T15:48:26Z-
dc.date.issued2016-
dc.identifier.citationThe DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. 2016, 354 (6313):765-768 Scienceen
dc.identifier.issn1095-9203-
dc.identifier.pmid27846608-
dc.identifier.doi10.1126/science.aaf7532-
dc.identifier.urihttp://hdl.handle.net/10033/621270-
dc.description.abstractAcute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents. Mechanistically, we found that AIM2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. Our results suggest that AIM2 may be a new therapeutic target for ionizing radiation exposure.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshApoptosisen
dc.subject.meshBone Marrowen
dc.subject.meshCaspase 1en
dc.subject.meshDNAen
dc.subject.meshDNA Breaks, Double-Strandeden
dc.subject.meshDNA-Binding Proteinsen
dc.subject.meshHematopoiesisen
dc.subject.meshInflammasomesen
dc.subject.meshIntestinal Mucosaen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshRadiation Injuriesen
dc.subject.meshRadiation, Ionizingen
dc.subject.meshWhole-Body Irradiationen
dc.titleThe DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalScience (New York, N.Y.)en
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