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The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury.
Hu, Bo Jin, Chengcheng Li, Hua-Bing Tong, Jiyu Ouyang, Xinshou Cetinbas, Naniye Malli Zhu, Shu Strowig, Till Lam, Fred C Zhao, Chen
Hu, Bo
Jin, Chengcheng
Li, Hua-Bing
Tong, Jiyu
Ouyang, Xinshou
Cetinbas, Naniye Malli
Zhu, Shu
Strowig, Till
Lam, Fred C
Zhao, Chen
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accepted manuscript
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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.
Citation
The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. 2016, 354 (6313):765-768 Science
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Journal
PubMed ID
PubMed Central ID
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Type
Article
Language
en
Description
Series/Report no.
ISSN
1095-9203