Center for Inflammation Research, VIB, Zwijnaarde B-9052, Belgium.
Department of Internal Medicine, Ghent University, Ghent B-9000, Belgium.
Cold Spring Harb Perspect Biol. 2019 Jan 2;11(1):a028563. doi: 10.1101/cshperspect.a028563.
As key regulators of both innate and adaptive immunity, it is unsurprising that the activity of interleukin (IL)-1 cytokine family members is tightly controlled by decoy receptors, antagonists, and a variety of other mechanisms. Additionally, inflammasome-mediated proteolytic maturation is a prominent and distinguishing feature of two important members of this cytokine family, IL-1β and IL-18, because their full-length gene products are biologically inert. Although vital in antimicrobial host defense, deregulated inflammasome signaling is linked with a growing number of autoimmune and autoinflammatory diseases. Here, we focus on introducing the diverse inflammasome types and discussing their causal roles in periodic fever syndromes. Therapies targeting IL-1 or IL-18 show great efficacy in some of these autoinflammatory diseases, although further understanding of the molecular mechanisms leading to unregulated production of these key cytokines is required to benefit more patients.
作为先天和适应性免疫的关键调节剂,白细胞介素 (IL)-1 细胞因子家族成员的活性受到诱饵受体、拮抗剂和多种其他机制的严格控制,这并不奇怪。此外,炎性体介导的蛋白水解成熟是该细胞因子家族两个重要成员(IL-1β 和 IL-18)的突出和显著特征,因为它们全长基因产物在生物学上是无活性的。尽管在抗菌宿主防御中至关重要,但失调的炎性体信号与越来越多的自身免疫和自身炎症性疾病有关。在这里,我们重点介绍不同类型的炎性体,并讨论它们在周期性发热综合征中的因果作用。针对 IL-1 或 IL-18 的治疗在一些自身炎症性疾病中显示出很好的疗效,尽管需要进一步了解导致这些关键细胞因子不受调节产生的分子机制,以使更多的患者受益。