Self-reactive IgE exacerbates interferon responses associated with autoimmunity.
Self-reactive IgE exacerbates interferon responses associated with autoimmunity.
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DOI：
10.1038/ni.3326
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发表时间：
2016-02
影响因子：
30.5
通讯作者：
Sanjuan MA
中科院分区：
文献类型：
--
作者：
Henault J;Riggs JM;Karnell JL;Liarski VM;Li J;Shirinian L;Xu L;Casey KA;Smith MA;Khatry DB;Izhak L;Clarke L;Herbst R;Ettinger R;Petri M;Clark MR;Mustelin T;Kolbeck R;Sanjuan MA
通常，IgE通过触发肥大细胞和嗜碱性粒细胞释放组胺和2型辅助细胞因子来介导过敏性免疫应答。在这里，我们报告说，在人类系统性红斑狼疮，特异性IgE抗体的双链DNA激活浆细胞样树突状细胞（pDC），一种免疫细胞类型与病毒防御，导致分泌大量的干扰素-α。患者血清中发现的dsDNA特异性IgE浓度与疾病严重程度相关，并通过FcεRI触发吞噬作用，随后通过吞噬体中Toll样受体9介导的DNA传感，极大地增强了pDC功能。这些发现扩展了已知的IgE介导的炎症的致病机制，超出了在过敏中发现的机制，并证明IgE可以触发能够加剧自我破坏性自身免疫反应的干扰素反应。
Canonically, IgE mediates allergic immune responses by triggering mast cells and basophils to release histamine and Type 2 helper cytokines. Here, we report that in human systemic lupus erythematosus, IgE antibodies specific for double-stranded DNA activate plasmacytoid dendritic cells (pDCs), an immune cell type linked to viral defense, leading to the secretion of substantial amounts of interferon-α. The concentrations of dsDNA-specific IgE found in patient serum correlated with disease severity and greatly potentiated pDC functions by triggering phagocytosis via FcεRI followed by Toll-like receptor 9-mediated DNA sensing in phagosomes. These findings expand the known pathogenic mechanisms of IgE-mediated inflammation beyond those found in allergy and demonstrate that IgE can trigger interferon responses capable of exacerbating self-destructive autoimmune responses.