Caspase-8: not so silently deadly.
Caspase-8: not so silently deadly.
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DOI：
10.1038/cti.2016.83
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发表时间：
2017-01
影响因子：
5.8
通讯作者：
Lawlor KE
中科院分区：
文献类型：
--
作者：
Feltham R;Vince JE;Lawlor KE
细胞凋亡是一种caspase依赖的程序性细胞死亡形式，通常被认为是一个免疫沉默的过程，是哺乳动物发育和维持细胞内稳态所必需的。相反，细胞死亡的裂解形式，如RIPK3和MLKL驱动的坏死性下垂，以及caspase-1/11依赖的下垂，被认为是通过释放损伤相关的分子模式(DAMP)来炎症的。最近，凋亡的caspase-8的功能已经扩展到对坏死性下垂的负性调节，直接或通过NLRP3炎症体将炎性白细胞介素1β(IL-1β)裂解成成熟的生物活性形式，以及调节细胞因子的转录反应。鉴于这些最新进展，由细胞死亡调控机制突变引起的人类自身炎症性疾病现在与不适当的炎症体激活有关。在这篇综述中，我们讨论了细胞死亡和先天性免疫细胞炎症信号之间的新的串扰，特别是caspase-8的新的非凋亡功能。我们还强调了与炎症小体功能增强相关的自体炎症性疾病的数量不断增加。
Apoptosis is a caspase-dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3- and MLKL-driven necroptosis, and caspase-1/11-dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase-8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin-1β (IL-1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses. In view of these recent advances, human autoinflammatory diseases that are caused by mutations in cell death regulatory machinery are now associated with inappropriate inflammasome activation. In this review, we discuss the emerging crosstalk between cell death and innate immune cell inflammatory signalling, particularly focusing on novel non-apoptotic functions of caspase-8. We also highlight the growing number of autoinflammatory diseases that are associated with enhanced inflammasome function.