The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury

Bo Hu, Chengcheng Jin, Hua Bing Li, Jiyu Tong, Xinshou Ouyang, Naniye Malli Cetinbas, Shu Zhu, Till Strowig, Fred C. Lam, Chen Zhao, Jorge Henao-Mejia, Omer Yilmaz, Katherine A. Fitzgerald, Stephanie C. Eisenbarth, Eran Elinav, Richard A. Flavell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)765-768
Number of pages4
JournalScience
Volume354
Issue number6313
DOIs
StatePublished - Nov 11 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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