The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
Department of Medicine, Division of Infectious Diseases and Immunology; Program in Innate Immunity
Immunology and Infectious Disease
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.
DOI of Published Version
Science. 2016 Nov 11;354(6313):765-768. Link to article on publisher's site
Science (New York, N.Y.)
Hu, Bo; Fitzgerald, Katherine A.; and Flavell, Richard A., "The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury" (2016). University of Massachusetts Medical School Faculty Publications. 1238.