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AIM2 in health and disease: Inflammasome and beyond.
Immunological Reviews ( IF 7.5 ) Pub Date : 2020-07-26 , DOI: 10.1111/imr.12903
Puja Kumari 1 , Ashley J Russo 1 , Sonia Shivcharan 1 , Vijay A Rathinam 1
Affiliation  

Nucleic acid sensing is a critical mechanism by which the immune system monitors for pathogen invasion. A set of germline‐encoded innate immune receptors detect microbial DNA in various compartments of the cell, such as endosomes, the cytosol, and the nucleus. Sensing of microbial DNA through these receptors stimulates, in most cases, interferon regulatory factor‐dependent type I IFN synthesis followed by JAK/STAT‐dependent interferon‐stimulated gene expression. In contrast, the detection of DNA in the cytosol by AIM2 assembles a macromolecular complex called the inflammasome, which unleashes the proteolytic activity of a cysteine protease caspase‐1. Caspase‐1 cleaves and activates the pro‐inflammatory cytokines such as IL‐1β and IL‐18 and a pore‐forming protein, gasdermin D, which triggers pyroptosis, an inflammatory form of cell death. Research over the past decade has revealed that AIM2 plays essential roles not only in host defense against pathogens but also in inflammatory diseases, autoimmunity, and cancer in inflammasome‐dependent and inflammasome‐independent manners. This review discusses the latest advancements in our understanding of AIM2 biology and its functions in health and disease.

中文翻译:

健康和疾病中的 AIM2:炎症小体及其他。

核酸感应是免疫系统监测病原体入侵的关键机制。一组由生殖系编码的先天免疫受体检测细胞内不同区域的微生物 DNA,例如内体、细胞质和细胞核。在大多数情况下,通过这些受体感知微生物 DNA 会刺激干扰素调节因子依赖性 I 型 IFN 合成,然后是 JAK/STAT 依赖性干扰素刺激的基因表达。相比之下,AIM2 检测胞质溶胶中的 DNA 组装了一个称为炎性体的大分子复合物,它释放了半胱氨酸蛋白酶 caspase-1 的蛋白水解活性。Caspase-1 裂解并激活促炎细胞因子,如 IL-1β 和 IL-18 以及一种成孔蛋白 gasdermin D,它会引发细胞焦亡,这是一种炎症形式的细胞死亡。过去十年的研究表明,AIM2 不仅在宿主防御病原体方面发挥着重要作用,而且在炎症性疾病、自身免疫和癌症中以炎症小体依赖和炎症小体独立的方式发挥着重要作用。本综述讨论了我们对 AIM2 生物学及其在健康和疾病中的功能的理解的最新进展。
更新日期:2020-08-28
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