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

Science. 2016 Nov 11;354(6313):765-768. doi: 10.1126/science.aaf7532.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / radiation effects*
  • Bone Marrow / metabolism
  • Bone Marrow / radiation effects
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • DNA / metabolism
  • DNA / radiation effects
  • DNA Breaks, Double-Stranded*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Hematopoiesis / drug effects
  • Hematopoiesis / genetics
  • Inflammasomes / genetics
  • Inflammasomes / metabolism*
  • Inflammasomes / radiation effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Radiation Injuries / genetics
  • Radiation Injuries / metabolism*
  • Radiation, Ionizing
  • Whole-Body Irradiation


  • Aim2 protein, mouse
  • DNA-Binding Proteins
  • Inflammasomes
  • DNA
  • Caspase 1