J Michelle Kahlenberg1, Mariana J Kaplan. 1. 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.
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
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