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炎性小体和细胞焦亡的新兴激活剂和调节剂。

Emerging Activators and Regulators of Inflammasomes and Pyroptosis.

机构信息

Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.

Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.

出版信息

Trends Immunol. 2019 Nov;40(11):1035-1052. doi: 10.1016/j.it.2019.09.005. Epub 2019 Oct 29.

Abstract

The inflammasome is a cytosolic immune signaling complex that induces inflammation and pyroptosis. Inflammasome complexes respond to a variety of pathogens, as well as danger or homeostasis-altering signals; they can play critical roles in the development of autoinflammatory conditions and cancer. Studies have now provided additional insights into the activation mechanisms and regulation of established inflammasome complexes, including NLRP1b, NLRP3, NOD-like receptor family apoptosis inhibitory protein (NAIP)-NLRC4, absent in melanoma (AIM)2, caspase-11, and pyrin. New activators and regulators of emerging NLRP6 and NLRP9b inflammasome complexes have also been described. We highlight the latest progress in our understanding of the molecular mechanisms governing inflammasome activation and pyroptosis, including the discovery of the pore-forming protein gasdermin D (GSDMD). We also discuss the importance of inflammasome activators and regulators in health and disease.

摘要

炎症小体是一种胞质免疫信号复合物,可诱导炎症和细胞焦亡。炎症小体复合物可响应多种病原体以及危险或改变内稳态的信号;它们在自身炎症性疾病和癌症的发展中可发挥关键作用。目前的研究为已确立的炎症小体复合物(包括 NLRP1b、NLRP3、NOD 样受体家族凋亡抑制蛋白(NAIP)-NLRC4、黑色素瘤缺失(AIM)2、半胱天冬酶-11 和 pyrin)的激活机制和调控提供了更多的见解。新兴的 NLRP6 和 NLRP9b 炎症小体复合物的新激活剂和调节剂也已被描述。我们重点介绍了我们对炎症小体激活和细胞焦亡的分子机制的最新理解,包括孔形成蛋白 gasdermin D(GSDMD)的发现。我们还讨论了炎症小体激活剂和调节剂在健康和疾病中的重要性。

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