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The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
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The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
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Journal Article
The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
2016
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Apoptosis - radiation effects
/ Bone Marrow - radiation effects
/ Cells
/ DNA
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Hematopoiesis - drug effects
/ Inflammasomes - radiation effects
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - radiation effects
/ Mice
/ Radiation Injuries - genetics
/ Radiation Injuries - metabolism
/ Tissues
