新加坡国立大学Lin-Fa Wang等研究人员合作发现，蝙蝠ASC2抑制炎性小体并改善炎症性疾病。该项研究成果发表在2023年5月11日出版的《细胞》杂志上。
研究人员表示，蝙蝠的特殊之处在于它们能够长寿，并能承载许多新出现的病毒。研究人员以前的研究表明，蝙蝠有不同的炎性小体，它是衰老和感染的核心角色。然而，炎性小体信号传导在对抗炎症性疾病中的作用仍不为人所知。
研究人员报告了蝙蝠ASC2是炎性小体的一个强有力的负向调节因子。蝙蝠ASC2在mRNA和蛋白水平上都高度表达，并且在抑制人类和小鼠炎性小体方面具有很强的效力。蝙蝠ASC2在小鼠中的转基因表达降低了痛风晶体和ASC颗粒诱导的腹膜炎的严重程度。蝙蝠ASC2还抑制了多种病毒诱发的炎症，并降低了甲型流感病毒感染的死亡率。重要的是，它还抑制了SARS-CoV-2免疫复合物诱导的炎性小体激活。四个关键残基被确定为蝙蝠ASC2的功能增益。这些研究结果表明，蝙蝠ASC2是炎性小体的一个重要的负调控因子，在炎症性疾病中具有治疗潜力。
附：英文原文
Title: Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases
Author: Matae Ahn, Vivian Chih-Wei Chen, Pritisha Rozario, Wei Lun Ng, Pui San Kong, Wan Rong Sia, Adrian Eng Zheng Kang, Qi Su, Lan Huong Nguyen, Feng Zhu, Wharton O.Y. Chan, Chee Wah Tan, Wan Shoo Cheong, Ying Ying Hey, Randy Foo, Fusheng Guo, Yan Ting Lim, Xin Li, Wan Ni Chia, Radoslaw M. Sobota, Nai Yang Fu, Aaron T. Irving, Lin-Fa Wang
Issue&Volume: 2023/05/11
Abstract: Bats are special in their ability to live long and host many emerging viruses. Ourprevious studies showed that bats have altered inflammasomes, which are central playersin aging and infection. However, the role of inflammasome signaling in combating inflammatorydiseases remains poorly understood. Here, we report bat ASC2 as a potent negativeregulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and proteinlevels and is highly potent in inhibiting human and mouse inflammasomes. Transgenicexpression of bat ASC2 in mice reduced the severity of peritonitis induced by goutcrystals and ASC particles. Bat ASC2 also dampened inflammation induced by multipleviruses and reduced mortality of influenza A virus infection. Importantly, it alsosuppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residueswere identified for the gain of function of bat ASC2. Our results demonstrate thatbat ASC2 is an important negative regulator of inflammasomes with therapeutic potentialin inflammatory diseases.
DOI: 10.1016/j.cell.2023.03.036
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00333-1