Kahlenberg J Michelle, Kaplan Mariana J
aDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan bSystemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Disorders, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Rheumatol. 2014 Sep;26(5):475-81. doi: 10.1097/BOR.0000000000000088.
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 the 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 the development of type I interferon responses, autoantibody production, and nephritis in the pristane model of lupus. The absence of melanoma 2 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.
在过去十年中，固有免疫在系统性红斑狼疮（SLE）中的作用一直是一个快速发展的研究领域。这一范畴包括这样一个概念，即炎性小体（一种激活半胱天冬酶 -1 进而激活细胞因子白细胞介素 -1β 和白细胞介素 -18 的分子复合物）的激活在狼疮发病机制中很重要。本综述将总结探索炎性小体机制在SLE中作用的最新发现。
免疫复合物可激活NLRP3炎性小体，且来源于SLE的巨噬细胞对固有免疫刺激反应过度，导致炎性小体激活增强和炎性细胞因子产生增加。多个小鼠模型的研究表明NLRP3炎性小体在介导狼疮性肾炎中起重要作用。半胱天冬酶 -1 作为炎性小体的核心酶，在狼疮的 pristane 模型中对I型干扰素反应、自身抗体产生及肾炎的发展至关重要。黑色素瘤 2 炎性小体的缺失在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，并且可能介导环境触发因素与狼疮发展之间的相互作用。进一步的研究应聚焦于抑制炎性小体成分是否可作为SLE治疗开发的可行靶点。
