細(xì)胞質(zhì)DNA是先天免疫系統(tǒng)的一個重要觸發(fā)器,。這一過程中所涉及的下游信號通道已被廣泛定性，但人們對其第一步,、即DNA的識別卻知之甚少,。

現(xiàn)在，在本期Nature上發(fā)表論文的兩個小組發(fā)現(xiàn)AIM2 (absent in melanoma 2) （“干擾素可誘導(dǎo)的HIN-200”家族的一個成員）是一個細(xì)胞質(zhì)DNA傳感器,。在有DNA存在時,，AIM2發(fā)生寡聚，并與銜接分子ASC結(jié)合來激發(fā)NF-κB 和半胱天冬酶-1——炎性體復(fù)合物的關(guān)鍵成分,。這說明AIM2炎性體是治療傳染病和自體免疫疾病的一個可能的目標(biāo),。（生物谷Bioon.com）

生物谷推薦原始出處：

Nature 458, 509-513 (26 March 2009) | doi:10.1038/nature07710

AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA

Teresa Fernandes-Alnemri1,2, Je-Wook Yu1,2, Pinaki Datta1, Jianghong Wu1 & Emad S. Alnemri1

1 Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
2 These authors contributed equally to this work.

Host- and pathogen-associated cytoplasmic double-stranded DNA triggers the activation of a NALP3 (also known as cryopyrin and NLRP3)-independent inflammasome1, which activates caspase-1 leading to maturation of pro-interleukin-1 and inflammation. The nature of the cytoplasmic-DNA-sensing inflammasome is currently unknown. Here we show that AIM2 (absent in melanoma 2), an interferon-inducible HIN-200 family member that contains an amino-terminal pyrin domain and a carboxy-terminal oligonucleotide/oligosaccharide-binding domain2, 3, senses cytoplasmic DNA by means of its oligonucleotide/oligosaccharide-binding domain and interacts with ASC (apoptosis-associated speck-like protein containing a CARD) through its pyrin domain to activate caspase-1. The interaction of AIM2 with ASC also leads to the formation of the ASC pyroptosome4, which induces pyroptotic cell death in cells containing caspase-1. Knockdown of AIM2 by short interfering RNA reduced inflammasome/pyroptosome activation by cytoplasmic DNA in human and mouse macrophages, whereas stable expression of AIM2 in the non-responsive human embryonic kidney 293T cell line conferred responsiveness to cytoplasmic DNA. Our results show that cytoplasmic DNA triggers formation of the AIM2 inflammasome by inducing AIM2 oligomerization. This study identifies AIM2 as an important inflammasome component that senses potentially dangerous cytoplasmic DNA, leading to activation of the ASC pyroptosome and caspase-1.