Cholera toxin B accelerates disease progression in lupus-prone mice by promoting lipid raft aggregation.
Cholera toxin B accelerates disease progression in lupus-prone mice by promoting lipid raft aggregation.
复制标题
霍乱毒素B通过促进脂质筏聚集来加速狼疮易发的疾病进展。
DOI：
10.4049/jimmunol.181.6.4019
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发表时间：
2008-09-15
期刊：
影响因子：
--
通讯作者：
Tsokos GC
中科院分区：
文献类型：
--
作者：
Deng GM;Tsokos GC
包括细菌和病毒在内的感染性因素被认为是自身免疫性疾病发展或恶化的诱因，包括遗传易感性个体中的系统性红斑狼疮。分子模仿和Toll样受体(TLR)的参与被赋予了有限的作用，将感染与自身免疫联系起来，但可能涉及其他机制。在这里，我们显示了狼疮易感小鼠的T细胞显示聚集的脂筏，其中含有信号、共刺激、炎症、黏附和TLR分子。带簇状脂筏的T细胞的百分比随着年龄的增长而增加，并且在狼疮病理发展之前达到峰值。我们发现霍乱毒素B，霍乱弧菌的一种成分，通过增强T细胞中的脂筏聚集，促进狼疮易感小鼠自身抗体的产生和肾小球肾炎。相反，脂筏聚集的破坏会导致疾病病理的延迟。我们的结果表明，脂筏对狼疮的发病有重要作用，并提供了一种新的机制，使聚集的脂筏成为感染与自身免疫之间的潜在联系。
Infectious agents including bacteria and viruses are thought to provide triggers for the development or exacerbation of autoimmune diseases including systemic lupus erythematosus in the genetically predisposed individual. Molecular mimicry and engagement of Toll-like receptors (TLR) have been assigned limited roles that link infection to autoimmunity but additional mechanisms are suspected to be involved. Here we show that T cells from lupus prone mice display aggregated lipid rafts which harbor signaling, costimulatory, inflammatory, adhesion and TLR molecules. The percentage of T cells with clustered lipid rafts increases with age and peaks prior to the development of lupus pathology. We show that cholera toxin B, a component of Vibrio cholerae promotes autoantibody production and glomerulonephritis in lupus-prone mice by enhancing lipid raft aggregation in T cells. In contrast, disruption of lipid raft aggregation results in delay of disease pathology. Our results demonstrate that lipid rafts contribute significantly to the pathogenesis of lupus and provide a novel mechanism whereby aggregated lipid rafts represent a potential link between infection to autoimmunity.
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