A novel type IIFN-producing cell subset in murine lupus
A novel type IIFN-producing cell subset in murine lupus
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DOI：
10.4049/jimmunol.180.7.5101
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Reeves, Westley H.
中科院分区：
文献类型：
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作者：
Lee, Pui Y.;Weinstein, Jason S.;Reeves, Westley H.
过量的I型干扰素（IFN-I）与系统性红斑狼疮（SLE）的发病机制有关。治疗用途（如果IFN-I可以触发发作。的SLE和大多数狼疮患者显示一组IFN刺激基因（ISG）的上调。尽管这种“IFN信号”与疾病活动、肾脏受累和自身抗体产生有关，但SLE中IFN-Ⅰ产生的来源仍不清楚。2，6，10，14-四甲基十五烷诱导的狼疮是目前唯一与IFN-I过量产生和ISG表达相关的SLE模型。在这项研究中，我们证明，四甲基十五烷治疗诱导积累的未成熟的Ly 6C（高）单核细胞，这是一个主要来源的IFN-I在这个狼疮模型。重要的是，它们与产生IFN的树突状细胞（DC）不同。单核细胞消耗迅速消除了IFN-I和ISG的表达，而DC的系统性消融几乎没有影响。此外，Ly 6C（高）mofiocyte的数量和狼疮自身抗体的产生之间有显着的相关性。因此，未成熟单核细胞而不是DC似乎是IFN-1依赖性狼疮模型中IFN-1的主要来源。
Excess type I IFNs (IFN-I) have been linked to the pathogenesis of systemic lupus erythematosus (SLE). Therapeutic use (if IFN-I can trigger the onset. of SLE and most lupus patients display up-regulation of a group of IFN-stimulated genes (ISGs). Although this "IFN signature" has been linked with disease activity, kidney involvement, and autoantibody production, the source of IFN-I production in SLE remains unclear. 2,6,10,14-Tetramethylpentadecane-induced lupus is at present the only model of SLE associated with excess IFN-I production And ISG expression. In this study, we demonstrate that tetramethylpentadecane treatment induces an accumulation of immature Ly6C(high) monocytes, which are a major source of IFN-I in this lupus model. Importantly, they were distinct from IFN-producing dendritic cells (DCs). The expression of IFN-I and ISGs was rapidly abolished by monocyte depletion whereas systemic ablation of DCs had little effect. In addition, there was a striking correlation between the numbers of Ly6C(high) mofiocytes and the production of lupus autoantibodies. Therefore, immature monocytes rather than DCs appear to be the primary source of IFN-I in this model of IFN-I-dependent lupus.