The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
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Author(s)
Hu, Bo
Jin, Chengcheng
Li, Hua-Bing
Tong, Jiyu
Ouyang, Xinshou
Zhu, Shu
Strowig, Till
Zhao, Chen
Henao-Mejia, Jorge
Fitzgerald, Katherine A.
Date Issued
November 2016
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Hu, Bo et al. “The DNA-Sensing AIM2 Inflammasome Controls Radiation-Induced Cell Death and Tissue Injury.” Science 354, 6313 (November 2016): 765–768 © 2016 American Association for the Advancement of Science
Version
Author's final manuscript
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1126/SCIENCE.AAF7532
