The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury.
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Authors
Hu, BoJin, 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
Issue Date
2016
Metadata
Show full item recordAbstract
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.Citation
The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. 2016, 354 (6313):765-768 ScienceAffiliation
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.Journal
Science (New York, N.Y.)PubMed ID
27846608Type
ArticleLanguage
enISSN
1095-9203ae974a485f413a2113503eed53cd6c53
10.1126/science.aaf7532
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
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