PDF(Pubmed)
Abstract：
The activation of the pyrin inflammasome represents a highly intriguing mechanism employed by the innate immune system to effectively counteract pathogenic agents. Despite its key role in innate immunity, pyrin has also garnered significant attention due to its association with a range of autoinflammatory diseases (AIDs) including familial Mediterranean fever caused by disruption of the MEFV gene, or in other genes involved in its complex regulation mechanisms. Pyrin activation is strictly dependent on homeostasis-altering molecular processes, mostly consisting of the disruption of the small Ras Homolog Family Member A (RhoA) GTPases by pathogen toxins. The downstream pathways are regulated by the phosphorylation of specific pyrin residues by the kinases PKN1/2 and the binding of the chaperone 14-3-3. Furthermore, a key role in pyrin activation is played by the cytoskeleton and gasdermin D, which is responsible for membrane pores in the context of pyroptosis. In addition, recent evidence has highlighted the role of steroid hormone catabolites and alarmins S100A8/A9 and S100A12 in pyrin-dependent inflammation. The aim of this article is to offer a comprehensive overview of the most recent evidence on the pyrin inflammasome and its molecular pathways to better understand the pathogenesis behind the significant group of pyrin-related AIDs.
摘要：
pyrin炎性体的激活代表了先天免疫系统用于有效抵抗病原体的非常有趣的机制。尽管它在先天免疫中起关键作用，pyrin也因其与一系列自身炎性疾病（AIDs）有关而引起了极大的关注，包括由MEFV基因破坏引起的家族性地中海热，或参与其复杂调控机制的其他基因。Pyrin激活严格依赖于改变体内平衡的分子过程，主要由病原体毒素对小Ras同源家族成员A（RhoA）GTP酶的破坏组成。下游途径受激酶PKN1/2对特定pyrin残基的磷酸化和伴侣14-3-3的结合调节。此外，在pyrin激活中起关键作用的是细胞骨架和gasderminD，在焦亡的情况下负责膜孔。此外,最近的证据强调了类固醇激素分解代谢产物和警报因子S100A8/A9和S100A12在pyrin依赖性炎症中的作用.本文的目的是提供有关pyrin炎性体及其分子途径的最新证据的全面概述，以更好地了解与pyrin相关的AIDs的重要群体背后的发病机理。
