IgG binds to desmoglein 3 in desmosomes and causes a desmosomal split without keratin retraction in a pemphigus mouse model
IgG binds to desmoglein 3 in desmosomes and causes a desmosomal split without keratin retraction in a pemphigus mouse model
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DOI：
10.1111/j.0022-202x.2004.22426.x
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发表时间：
2004-05-01
影响因子：
6.5
通讯作者：
Nishikawa, T
中科院分区：
文献类型：
--
作者：
Shimizu, A;Ishiko, A;Nishikawa, T
寻常天疱疮（PV）是由抗桥粒芯糖蛋白3（Dsg 3）的IgG自身抗体引起的自身免疫性起泡疾病。在这项研究中，我们的特点是在体内结合的IgG，Dsg3，和桥斑蛋白在棘层松解的过程中，在一个活跃的小鼠PV模型的超微结构定位，使用包埋后免疫电镜。在角质形成细胞接触的非棘层松解区域中，IgG标记仅限于桥粒的细胞外部分，并且均匀地分布在桥粒的整个长度上。体内IgG的分布与对照小鼠中抗Dsg3标记的分布相似。在棘层松解区内，有大量的分裂桥粒，角蛋白丝插入桥粒附着斑。这些分裂桥粒细胞外区域也装饰有抗Dsg3 IgG，并与其细胞质附着斑中的桥粒斑蛋白染色相关。没有观察到明显的不含IgG标记的分裂桥粒，表明在体内棘层松解开始之前Dsg3没有从桥粒中耗尽。桥粒样结构（无角蛋白插入）只发现在基底细胞的侧面，而不是在棘层松解分裂的网站上的顶面。这些发现表明，抗Dsg3 IgG抗体可以直接进入体内桥粒中存在的Dsg3，并引起随后的桥粒分离，导致PV中的水疱形成。
Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by IgG autoantibodies against desmoglein 3 (Dsg3). In this study, we characterized the ultrastructural localization of in vivo-bound IgG, Dsg3, and desmoplakin during the process of acantholysis in an active mouse PV model, using post-embedding immunoelectron microscopy. In non-acantholytic areas of keratinocyte contact, IgG labeling was restricted to the extracellular part of desmosomes, and was evenly distributed throughout the entire length of the desmosome. The distribution of in vivo IgG was similar to that of anti-Dsg3 labeling in the control mouse. Within the acantholytic areas, there were abundant split-desmosomes with keratin filaments inserted into the desmosomal attachment plaques. These split-desmosome extracellular regions were also decorated with anti-Dsg3 IgG and were associated with desmoplakin staining in their cytoplasmic attachment plaques. No apparent split-desmosomes, free of IgG-labeling were observed, suggesting that Dsg3 was not depleted from the desmosome before the start of acantholysis in vivo. Desmosome-like structures (without keratin insertion) were found only on the lateral surfaces of basal cells, but not on the apical surfaces at the site of acantholytic splits. These findings indicate that anti-Dsg3 IgG antibodies can directly access Dsg3 present in desmosomes in vivo and cause the subsequent desmosome separation that leads to blister formation in PV.