The inflammasome and lupus: another innate immune mechanism contributing to disease pathogenesis?
The inflammasome and lupus: another innate immune mechanism contributing to disease pathogenesis?
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DOI：
10.1097/bor.0000000000000088
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发表时间：
2014-09
影响因子：
5.1
通讯作者：
Kaplan MJ
中科院分区：
文献类型：
--
作者：
Kahlenberg JM;Kaplan MJ
先天免疫在系统性红斑狼疮（SLE）中的作用在过去十年中一直是一个快速扩展的研究领域。该标题中包含的概念是，炎性体（一种激活半胱天冬酶-1进而激活细胞因子IL-1β和IL-18的分子复合物）的激活在狼疮发病机制中很重要。本文将总结最近的发现，探索炎症机制在系统性红斑狼疮的作用。免疫复合物可以激活NLRP 3炎性体，并且SLE衍生的巨噬细胞对先天性免疫刺激具有高反应性，导致炎性体的活化增强和炎性细胞因子的产生。在几种鼠模型中的工作表明NLRP 3炎性体在介导狼疮肾炎中的重要作用。Caspase-1是炎性体的中心酶，对于狼疮降植烷模型中I型干扰素反应、自身抗体产生和肾炎的发展至关重要。AIM 2炎性小体在SLE中可能具有保护和致病作用。最近的证据表明，炎性小体机制在SLE中失调，在促进器官损伤中起重要作用，并可能介导环境触发因素与狼疮发展之间的相互作用。进一步的研究应该集中在抑制炎性体成分是否可以作为SLE治疗发展的一个可行的目标。
The role of innate immunity in systemic lupus erythematosus (SLE) has been a rapidly expanding area of research over the last decade. Included in this rubric is the concept that activation of the inflammasome, a molecular complex that activates caspase-1 and in turn, the cytokines IL-1β and IL-18, is important in lupus pathogenesis. This review will summarize recent discoveries exploring the role of the inflammasome machinery in SLE. Immune complexes can activate the NLRP3 inflammasome, and SLE-derived macrophages are hyper-responsive to innate immune stimuli, leading to enhanced activation of the inflammasome and production of inflammatory cytokines. Work in several murine models suggests an important role for the NLRP3 inflammasome in mediating lupus nephritis. Caspase-1, the central enzyme of the inflammasome, is essential for development of type I interferon responses, autoantibody production and nephritis in the pristane model of lupus. The AIM2 inflammasome may have protective and pathogenic roles in SLE. Recent evidence suggests that the inflammasome machinery is dysregulated in SLE, plays an important role in promotion of organ damage, and may mediate cross-talk between environmental triggers and the development of lupus. Further research should focus on whether inhibition of inflammasome components may serve as a viable target for therapeutic development in SLE.