寻常型天疱疮及其活动性疾病小鼠模型。

Masayuki Amagai
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引用次数: 27

摘要

天疱疮是一种皮肤和粘膜的自身免疫性疾病,由抗桥粒蛋白(Dsg)的IgG自身抗体介导,桥粒蛋白是一种钙粘蛋白型细胞-细胞粘附分子。最近,用一种独特的方法,用自身抗原敲除小鼠建立了寻常型天疱疮(PV)的活动性疾病小鼠模型,该模型不获得缺陷基因产物的自我耐受性。该方法包括将Dsg3-/-淋巴细胞过继转移到表达Dsg3-的Rag2-/-免疫缺陷小鼠中,诱导其稳定产生致病性抗Dsg3 IgG超过6个月,并在受体小鼠中形成典型组织学的PV表型,包括口腔糜坏。随后,从PV模型小鼠中制备AK和NAK系列抗dsg3 IgG单克隆抗体。这些单克隆抗体在水疱形成中表现出致病异质性,这至少在一定程度上可以解释为它们的表位,以及通过结合在分子不同部分反应的几种单克隆抗体而产生的协同致病作用。虽然该模型不能反映自身免疫性疾病的实际触发因素,但它确实提供了一种方法来研究T和B淋巴细胞在持续自身抗体产生中的作用,并澄清自身免疫性疾病中尚未解决的免疫机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pemphigus vulgaris and its active disease mouse model.

Pemphigus is an autoimmune disease of the skin and mucous membranes and is mediated by IgG autoantibodies against desmoglein (Dsg), a cadherin-type cell-cell adhesion molecule in desmosomes. Recently, an active disease mouse model of pemphigus vulgaris (PV) was generated with a unique approach using autoantigen knockout mice, in which selftolerance of the defective gene product is not acquired. This approach included the adoptive transfer of Dsg3-/- lymphocytes to Rag2-/- immunodeficient mice that express Dsg3- induced stable production of pathogenic anti-Dsg3 IgG for over 6 months and the phenotype of PV including oral erosion with the typical histology in recipient mice. Subsequently, AK and NAK series of anti-Dsg3 IgG monoclonal antibodies were developed from the PV model mice. These monoclonal antibodies showed pathogenic heterogeneity in blister formation, which is, at least in part, explained by their epitopes, and synergistic pathogenic effects by combining several monoclonal antibodies reacting in different parts of the molecule. Although this model does not reflect the actual triggers of autoimmune diseases, it does provide a means to investigate the roles of T and B lymphocytes in perpetuating autoantibody production and to clarify unsolved immunological mechanisms in the autoimmune diseases.

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