TY - JOUR
T1 - The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
AU - Hu, Bo
AU - Jin, Chengcheng
AU - Li, Hua Bing
AU - Tong, Jiyu
AU - Ouyang, Xinshou
AU - Cetinbas, Naniye Malli
AU - Zhu, Shu
AU - Strowig, Till
AU - Lam, Fred C.
AU - Zhao, Chen
AU - Henao-Mejia, Jorge
AU - Yilmaz, Omer
AU - Fitzgerald, Katherine A.
AU - Eisenbarth, Stephanie C.
AU - Elinav, Eran
AU - Flavell, Richard A.
N1 - Funding Information:
We thank V. M. Dixit, N. Kayagaki, and E. S. Alnemri for sharing materials and reagents, and V. A. Rathinam for technical advice. We thank P. Bongiorni for assistance with radiation experiments. The data presented in this manuscript are tabulated in the main paper and in the supplementary materials. H.-B.L. is supported by NIH T32 2T32DK007356. This work was supported by the Howard Hughes Medical Institute (R.A.F.).
Publisher Copyright:
© 2016, American Association for the Advancement of Science. All rights reserved.
PY - 2016/11/11
Y1 - 2016/11/11
N2 - 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.
AB - 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.
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U2 - 10.1126/science.aaf7532
DO - 10.1126/science.aaf7532
M3 - Article
C2 - 27846608
AN - SCOPUS:84994507182
SN - 0036-8075
VL - 354
SP - 765
EP - 768
JO - Science
JF - Science
IS - 6313
ER -