Apoptosis and NET formation in the pathogenesis of SLE
Apoptosis and NET formation in the pathogenesis of SLE
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DOI：
10.3109/08916934.2012.719953
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发表时间：
2012-12-01
期刊：
影响因子：
3.5
通讯作者：
Van der Vlag, Johan
中科院分区：
文献类型：
--
作者：
Bouts, Yvette M.;Wolthuis, David F. G. J.;Van der Vlag, Johan
系统性红斑狼疮是一种自身免疫性疾病，其特征在于形成抗核自身抗体，特别是抗染色质抗体。虽然这种疾病的病因尚未完全阐明，但已提出涉及几种机制。由于异常凋亡或凋亡细胞的去除减少，释放含有染色质的凋亡泡。在细胞凋亡过程中，染色质被修饰，增加其免疫原性。髓样树突状细胞（myDC）可以吸收凋亡的水泡并刺激自身反应性T辅助细胞，随后通过自身反应性B细胞形成自身抗体。由抗染色质自身抗体和修饰的染色质形成的免疫复合物存款在基底膜上，并激发局部炎症，但也可以刺激浆细胞样树突状细胞产生IFN-α。除了凋亡性大疱之外，在称为NETosis的过程中，由垂死的中性粒细胞释放的中性粒细胞胞外陷阱也可以作为自身抗原的来源。在这篇综述中，我们描述了细胞凋亡和NETosis在SLE发病机制中的作用，并展示了这两个过程如何相互作用。
Systemic Lupus Erythematosus is an autoimmune disease characterized by the formation of anti-nuclear autoantibodies, particularly anti-chromatin. Although the aetiology of the disease has not yet been fully elucidated, several mechanisms have been proposed to be involved. Due to an aberrant apoptosis or decreased removal of apoptotic cells, apoptotic blebs containing chromatin are released. During apoptosis, chromatin is modified that increases its immunogenicity. Myeloid dendritic cells (myDC) can take up apoptotic blebs and stimulate autoreactive T helper cells, and subsequently the formation of autoantibodies by autoreactive B cells. Immune complexes formed by anti-chromatin autoantibodies and modified chromatin deposit on basal membranes, and incite a local inflammation, but can also stimulate plasmacytoid dendritic cells to produce IFN-alpha. In addition to apoptotic blebs, neutrophil extracellular traps released by dying neutrophils, in a process called NETosis, may serve as a source of autoantigens as well. In this review, we describe the role of both apoptosis and NETosis in the pathogenesis of SLE, and show how both processes may interact with each other.