School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld, Australia.
EMBO Rep. 2019 Sep;20(9):e48891. doi: 10.15252/embr.201948891. Epub 2019 Aug 5.
The non-canonical inflammasome mediates pyroptotic cell death in response to bacterial lipopolysaccharide (LPS) found in the cytosol. Understanding the mechanism and regulation of this system is of great interest, given its central role in mouse models of bacterial septic shock. In this issue of EMBO Reports, Benaoudia and colleagues sought to discover extra players in the human non-canonical inflammasome using a CRISPR library screen; the only strongly positive hit apart from the known components caspase-4 and gasdermin D was interferon regulatory factor-2 (IRF2) [ ]. IRF2 was found to be a transcriptional activator of caspase-4, and in its absence, induction of IRF1 could substitute to maintain caspase-4 expression.
细胞质中存在的细菌脂多糖 (LPS) 会激活非经典的炎性小体，引发细胞发生细胞焦亡。鉴于该系统在细菌性脓毒症休克的小鼠模型中起着核心作用，了解该系统的作用机制和调控机制非常重要。在本期《EMBO 报告》中，Benaoudia 及其同事使用 CRISPR 文库筛选，试图在人类非经典炎性小体中发现其他成员；除了已知的成分胱天蛋白酶-4 和 GSDMD 外，唯一的强烈阳性命中是干扰素调节因子-2（IRF2）[ ]。IRF2 被发现是胱天蛋白酶-4 的转录激活因子，在其缺失的情况下，IRF1 的诱导可以替代它来维持胱天蛋白酶-4 的表达。
