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

Bo Hu | Zendy; Chengcheng Jin | Zendy; Huabing Li | Zendy; Jiyu Tong | Zendy; Xinshou Ouyang | Zendy; Naniye Mallı Cetinbas | Zendy; Shu Zhu | Zendy; Till Strowig | Zendy; Fred C. Lam | Zendy; Chen Zhao | Zendy; Jorge HenaoMejia | Zendy; Ömer Yılmaz | Zendy; Katherine A. Fitzgerald | Zendy; Stephanie C. Eisenbarth | Zendy; Eran Elinav | Zendy; Richard A. Flavell | Zendy

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

Author(s) -

Bo Hu,

Chengcheng Jin,

Huabing Li,

Jiyu Tong,

Xinshou Ouyang,

Naniye Mallı Cetinbas,

Shu Zhu,

Till Strowig,

Fred C. Lam,

Chen Zhao,

Jorge HenaoMejia,

Ömer Yılmaz,

Katherine A. Fitzgerald,

Stephanie C. Eisenbarth,

Eran Elinav,

Richard A. Flavell

Publication year - 2016

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aaf7532

Subject(s) - aim2 , inflammasome , dna damage , programmed cell death , ionizing radiation , gastrointestinal tract , apoptosis , bone marrow , cancer research , biology , haematopoiesis , microbiology and biotechnology , dna , immunology , inflammation , stem cell , irradiation , genetics , biochemistry , physics , nuclear physics

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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