An Update on Autoinflammatory Diseases: Inflammasomopathies
An Update on Autoinflammatory Diseases: Inflammasomopathies
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DOI：
10.1007/s11926-018-0750-4
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发表时间：
2018-07-01
影响因子：
5
通讯作者：
Masters, Seth L.
中科院分区：
文献类型：
--
作者：
Harapas, Cassandra R.;Steine, Annemarie;Masters, Seth L.
综述目的自体炎症性疾病是由异常的先天免疫激活引起的。在炎症性疾病的情况下，这些都可归因于由NLRP3等先天免疫传感器核化的炎症体复合体的激活。这篇综述将集中在有助于阐明另外三种感受器(NLRP1、NLRC4和PYRIN)也可引起炎症的作用的最新进展。最近发现的PYRIN(S242R或E244K)突变破坏了抑制性14-3-3结合位点，并导致新特征的PYRIN相关性自身炎症伴中性粒细胞皮肤病(PAAND)。此外，甲氧戊酸激酶缺乏引起的另一种自体炎症性疾病导致RhoGTP酶预烯基化缺陷和随后的比林S242R磷酸化丢失，这表明疾病的共同机制。其他炎症体，如NLRP1和NLRC4，最近发现了新的突变，这些突变提供了激活和自身抑制所需的特定结构域的信息。本文综述了炎症性男性疾病研究的最新进展，重点介绍了阐明新致病机制的基因发现。
Purpose of Review Autoinflammatory diseases are driven by abnormal innate immune activation. In the case of inflammasomopathies, these are all attributable to activation of an inflammasome complex, nucleated by an innate immune sensor such as NLRP3. This review will focus on recent advances that have helped to elucidate the role of three other sensors (NLRP1, NLRC4 and pyrin) which can also cause inflammasomopathies.Recent Findings Mutations in pyrin (S242R or E244K) destroy an inhibitory 14-3-3 binding site and result in the newly characterised disease pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Moreover, a separate autoinflammatory disease driven by mevalonate kinase deficiency leads to defective RhoGTPase prenylation and subsequent loss of pyrin S242R phosphorylation, suggesting a shared mechanism of disease. Other inflammasomes such as NLRP1 and NLRC4 have had novel mutations described recently, which inform about the specific domains required for activation and autoinhibition.Summary This review covers recent advances in the study of inflammasomopathies, focussing on gene discoveries that elucidate new pathogenic mechanisms.